|
Homologous physiological effects of phenformin and
chromium picolinate.
McCarty MF
Nutrition 21, San Diego, CA 92109.
Med Hypotheses (England) Oct 1993, 41 (4)
p316-24
The insulin-sensitizing drug phenformin, in addition to its
clinical utility in type II diabetes, has been reported to
lower blood lipids, reduce body fat, enhance cellular
immunity, and--in rodents--to increase mean lifespan and
retard the development of growth of cancer. Initial studies
with the insulin-sensitizing nutrient chromium picolinate
indicate that it aids glucose tolerance in type II diabetes,
lowers elevated LDL cholesterol, reduces body fat while
increasing lean mass, and-- in rats--increases median
lifespan. These effects are thus analogous to those reported
for phenformin; chromium picolinate should be tested to
determine whether it likewise has a favorable impact on
cellular immunity and cancer risk. The ability of both
phenformin and chromium picolinate to increase lifespan
suggests that age-related insulin resistance may play a
profound role in the aging process. It may not be coincidental
that caloric restriction--the best documented technique for
increasing lifespan--markedly increases insulin sensitivity.
Safe, appropriate measures for promoting lifelong insulin
sensitivity include a low-fat diet, exercise training, and
supplemental chromium picolinate. (75 Refs.)
[The effect of chromium picolinate on the liver
levels of trace elements]
Aguilar MV; Jorge AM; Mateos CJ; Garcia J; Laborda JM;
Meseguer I; Martinez-Para MC; Gonzalez MJ
Departamento de Nutricion y Bromatologia, Facultad de
Farmacia, Universidad de Alcala de Henares, Espana.
Nutr Hosp (Spain) Nov-Dec 1995, 10 (6) p373-6
Chromium picolinate has been implicated as a lipid and
carbohydrate reducing agent, and therefore it may be a
valuable adjunct to the treatment and prevention of diabetes
and heart disease. This compound is inexpensive and apparently
nontoxic. In this work, we have determined the influence of
its administration (100, 200, 500 micrograms Cr/ml, for 7 and
21 days) on hepatic content of Zn, Mn, Cu and Fe of male
Wistar rats. The results show a variation of the levels of
these elements after the administration of chromium
picolinate, although the differences are only significantly (p
< 0.01) in the case of Mn. This influence is
dose-dependent, occurring a decrease of 72% in the group
treated with 500 micrograms/ml (Pic-500) respect to the
content of control group.
Anabolic effects of insulin on bone suggest a role
for chromium picolinate in preservation of bone density.
McCarty MF
Med Hypotheses (England) Sep 1995, 45 (3) p241-6
Activation of osteoclasts by parathyroid hormone (PTH) is
mediated by PTH stimulation of osteoblasts, and is dependent
on a PTH-induced rise in protein kinase C activity.
Physiological levels of insulin reduce the ability of PTH to
activate protein kinase C in osteoblasts, suggesting that
insulin may be a physiological antagonist of bone resorption.
In addition, insulin is known to promote collagen production
by osteoblasts. These findings imply that efficient insulin
activity may exert an anabolic effect on bone, and rationalize
the many clinical studies demonstrating reduced bone density
in Type I diabetes. Recently, the insulin-sensitizing nutrient
chromium picolinate has been found to reduce urinary excretion
of hydroxyproline and calcium in postmenopausal women,
presumably indicative of a reduced rate of bone resorption.
This nutrient also raised serum levels of
dehydroepiandrosterone-sulfate, which may play a physiological
role in the preservation of postmenopausal bone density. The
impact of chromium picolinate (alone or in conjunction with
calcium and other micronutrients) on bone metabolism and bone
density, merits further evaluation in controlled studies. (69
Refs.)
Longevity effect of chromium
picolinate--'rejuvenation' of hypothalamic function?
McCarty MF
Nutrition 21, San Diego, California 92109.
Med Hypotheses (England) Oct 1994, 43 (4)
p253-65
The first rodent longevity study with the
insulin-sensitizing nutrient chromium picolinate has reported
a dramatic increase in both median and maximal lifespan.
Although the observed moderate reductions in serum glucose
imply a decreased rate of tissue glycation reactions, it is
unlikely that this alone can account for the substantial
impact on lifespan; an effect on central neurohormonal
regulation can reasonably be suspected. Recent studies
highlight the physiological role of insulin as a modulator of
brain function. I postulate that aging is associated with a
reduction of effective insulin activity in the brain, and this
contributes to age-related alterations of hypothalamic
functions that result in an 'older' neurohormonal milieu;
consistent with this possibility, diabetes leads to changes of
hypothalamic regulation analogous to those seen in normal
aging. Conversely, promoting brain insulin activity with
chromium picolinate may help to maintain the hypothalamus in a
more functionally youthful state; increased hypothalamic
catecholamine activity, sensitization of insulin-responsive
central mechanisms regulating appetite and thermogenesis, and
perhaps trophic effects on brain neurons may play a role in
this regard. Since both the pineal gland and thymus are
dependent on insulin activity, chromium may aid their function
as well. Thus, the longevity effect of chromium picolinate may
depend primarily on delay or reversal of various age-related
changes in the body's hormonal and neural milieu. A more
general strategy of hypothalamic 'rejuvenation' is proposed
for extending healthful lifespan.
Thiamine pyrophosphate and pyridoxamine inhibit the
formation of antigenic advanced glycation end-products:
comparison with aminoguanidine.
Booth AA; Khalifah RG; Hudson BG
Department of Biochemistry and Molecular Biology, University
of Kansas Medical Center, Kansas City, Kansas 66160-7421,
USA.
Biochem Biophys Res Commun (United States) Mar 7 1996, 220
(1) p113-9
Nonenzymatic glycation of proteins by glucose leading to
the formation of toxic and immunogenic advanced glycation end
products (AGEs) may be a major contributor to the pathological
manifestations of diabetes mellitus, aging, and, possibly,
neurodegenerative diseases such as Alzheimer's. We tested the
in vitro inhibition of antigenic AGE formation on bovine serum
albumin, ribonuclease A, and human hemoglobin by various
vitamin B1 and B6 derivatives. Among the inhibitors,
pyridoxamine and thiamine pyrophosphate potently inhibited AGE
formation and were more effective than aminoguanidine,
suggesting that these two compounds may have novel therapeutic
potential in preventing vascular complications of diabetes. An
unexpected finding was that aminoguanidine inhibited the late
kinetic stages of glycation much more weakly than the early
phase.
Loss of glucose-induced insulin secretion and GLUT2
expression in transplanted beta-cells.
Ogawa Y; Noma Y; Davalli AM; Wu YJ; Thorens B; Bonner-Weir S;
Weir GC
E.P. Joslin Laboratories, Joslin Diabetes Center, Boston, MA
02215.
Diabetes (United States) Jan 1995, 44 (1) p75-9
Either 200 or 400 syngeneic islets were transplanted under
the kidney capsule of normal or streptozocin-induced diabetic
B6/AF1 mice. The diabetic mice with 400 islets became
normoglycemic, but those with 200 islets, an insufficient
number, were still diabetic after the transplantation (Tx).
Two weeks after Tx, GLUT2 expression in the islet grafts was
evaluated by immunofluorescence and Western blots, and graft
function was examined by perfusion of the graft-bearing
kidney. Immunofluorescence for GLUT2 was dramatically reduced
in the beta-cells of grafts with 200 islets exposed to
hyperglycemia. However, it was plentiful in grafts with 400
islets in a normoglycemic environment. Densitometric analysis
of Western blots on graft homogenates demonstrated that GLUT2
protein levels in the islets, when exposed to chronic
hyperglycemia for 2 weeks, were decreased to 16% of those of
normal recipients. Moreover, these grafts had defective
glucose-induced insulin secretion, while the effects of
arginine were preserved. We conclude that GLUT2 expression in
normal beta-cells is promptly down-regulated during exposure
to hyperglycemia and may contribute to the loss of
glucose-induced secretion of diabetes.
Case report: amelioration of insulin resistance in
diabetes with dehydroepiandrosterone.
Buffington CK; Pourmotabbed G; Kitabchi AE
Department of Medicine, University of Tennessee,
Memphis.
Am J Med Sci (United States) Nov 1993, 306 (5)
p320-4
In hyperandrogenic females, the ratio of
dehydroepiandrosterone (DHEA) to testosterone may be an
important determinant of insulin sensitivity. This study
involved changes in insulin sensitivity and glucose metabolism
with therapeutic manipulation of DHEA (S)/testosterone in a
female patient with non-insulin-dependent diabetes and
hyperandrogenism. Therapeutic intervention included 1-month
treatment with 0.25 mg dexamethasone at bedtime and 1-month
dexamethasone + DHEA. Insulin sensitivity and glucose
tolerance were assessed before and after each treatment
regimen by examining: 1) fasting and oral glucose tolerance
test glucose and insulin levels, 2) hypoglycemic response to
intravenous insulin, and 3) erythrocyte insulin receptor
binding. With dexamethasone alone, DHEAS, testosterone, and
their ratio were reduced with a concomitant increase (30%) in
oral glucose tolerance test insulin levels and a decrease
(33%) in erythrocyte insulin binding. With DHEA +
dexamethasone, the ratio of DHEAS/testosterone increased
16-fold along with a marked improvement in insulin
sensitivity, as determined by a more than 30% reduction in
fasting and oral glucose tolerance test insulin levels, a
threefold stimulation of the rate of glucose disappearance
with intravenous insulin, and a 30% increase in insulin
binding. DHEA improved insulin sensitivity and reduced fasting
and oral glucose tolerance test glucose levels and ameliorated
the diabetic state. The ratio of DHEAS/testosterone is an
important regulator of insulin sensitivity and glucose
tolerance and that DHEA therapy may be beneficial in the
treatment of certain forms of insulin resistance.
Therapeutic effects of dehydroepiandrosterone
metabolites in diabetes mutant mice (C57BL/KsJ-db/db).
Coleman DL; Leiter EH; Applezweig N
Endocrinology 1984 Jul;115(1):239-43
Dehydroepiandrosterone (DHEA) fed at 0.4% in the diet is
known to exert strong antihyperglycemic effects in C57BL/KsJ
genetically diabetic (db/db) mice. Three of the major
metabolic products of DHEA; DHEA sulfate,
alpha-hydroxyetiocholanolone (alpha-ET), and beta-
hydroxyetiocholanolone (beta-ET) when fed at 0.1% in the diet,
and one putative product, 17 beta-estradiol, when fed at
0.005% also prevented the development of severe diabetes while
having little effect on the amount of food eaten or the rate
of weight gain. When suboptimal doses (5-20 micrograms/week)
of estradiol were injected in combination with diets
containing either alpha-ET or beta-ET, marked potentiating
effect was noted, normalization of the hyperglycemia being
produced with as little as 0.025% of beta-ET and 0.05% of
alpha-ET. The ability of the etiocholanolones to maintain
islet integrity and prevent the development of most diabetes
symptoms suggests that these metabolites are not merely
inactive end products of steroid metabolism, but are
physiological effectors in their own right.
The endocrine pancreas in pyridoxine deficient
rats.
Toyota T; Kai Y; Kakizaki M; Ohtsuka H; Shibata Y; Goto Y
Tohoku
Med (Japan) Jul 1981, 134 (3) p331-6
Because the supplementation of pyridoxine (vitamin B6)
improves the glucose tolerance in gestational diabetes and
adult onset diabetes, pyridoxine deficiency has been
considered to be one of the factors that cause diabetes
mellitus. We produced pyridoxine deficient rats by giving
pyridoxine-free food with deoxypyridoxine which competitively
the activity of pyridoxal phosphate. In these pyridoxine
deficient rats plasma insulin during the glucose tolerance
test was significantly low as compared with controls. In vitro
experiments of pancreas perfusion showed that secretion of
insulin and glucagon was impaired in the pyridoxine
deficiency. Since the restriction of diet-calorie caused a
decrease in arginine- nduced secretion of insulin and glucagon
from the isolated pancreas, the impairment of the endocrine
pancreas may depend on malnutrition. Pyridoxine deficiency is
surely one of the factors that impair the endocrine pancreas
by multifactorial derangement of metabolism besides the
tryptophan-nicotinic acid pathway.
Vitamin B6 metabolism and diabetes.
Rogers KS; Mohan C
Department of Biochemistry, Purdue University, West
Lafayette, Indiana 47907.
Biochem Med Metab Biol (United States) Jun 1994, 52 (1)
p10-7
No abstract.
A deficiency of vitamin B6 is a plausible molecular
basis of the retinopathy of patients with diabetes
mellitus.
Ellis JM; Folkers K; Minadeo M; VanBuskirk R; Xia LJ;
Tamagawa H
Department of Medicine, Titus County Hospital, Mt. Pleasant,
Texas.
Biochem Biophys Res Commun (United States) Aug 30 1991, 179
(1) p615-9
Eighteen patients with diabetes mellitus, some of whom had
variously retinopathy, pregnancy, and the carpal tunnel
syndrome, and were variously treated with steroids and vitamin
B6, have been overviewed for periods of 8 months to 28 years.
We have established an association of a deficiency of vitamin
B6 with diabetes by monitoring the specific activity of the
erythrocyte glutamic oxaloacetic transaminase and again by the
association with the carpal tunnel syndrome (C.T.S.). It has
been known for a decade that C.T.S. is caused by a B6
deficiency. The absence of retinopathy in vitamin B6-treated
diabetic patients over periods of 8 months - 28 years appears
monumental. These observations are like discovery and
constitute a basis for a new protocol to establish the
apparent relationship of a deficiency of vitamin B6 as a
molecular cause of diabetic neuropathy. Blindness and vision
are so important that the strength or weakness of the
observations are not important; the conduct of a new protocol
is important.
Erythrocyte O2 transport and metabolism and effects
of vitamin B6 therapy in type II diabetes mellitus.
Solomon LR; Cohen K
Department of Medicine, Veterans Administration Medical
Center, West Haven, CT 06516.
Diabetes (United States) Jul 1989, 38 (7) p881-6
The effects of vitamin B6 on erythrocyte metabolism,
erythrocyte hemoglobin O2 affinity (P50), and nonenzymatic
glycosylation were studied in 15 Caucasian men with type II
(non-insulin-dependent) diabetes mellitus. A control group of
13 healthy Caucasian men was also evaluated. Before treatment,
diabetic subjects had low mean cell hemoglobin concentration
values and increases in both erythrocyte
2,3-diphosphoglycerate (2,3-DPG) levels and erythrocyte
hexokinase activities. Although all three of these changes are
associated with a decrease in hemoglobin O2 (Hb-O2) affinity,
P50 values were normal in diabetic subjects. Moreover, P50
values normalized to pH 7.4 (P50(7.4] were inversely related
to the level of glycosylated hemoglobin (HbA1c). Both
erythrocyte 2,3-DPG and erythrocyte ATP were also inversely
related to HbA1c. Vitamin B6 nutriture, as determined by
erythrocyte aspartate aminotransferase (AST) and alanine
aminotransferase (ALT) activities, was normal in all diabetic
subjects before vitamin B6 therapy. Nonetheless, HbA1c levels
decreased after 6 wk of treatment with 150 mg/day pyridoxine
and increased again during placebo administration. These
changes were not explained by changes in fasting blood
glucose. Pyridoxine therapy also decreased P50(7.4) values and
increased erythrocyte AST and ALT activities but had no effect
on 2,3-DPG, ATP, or the activities of hexokinase,
glucose-6-phosphate dehydrogenase, and 6-phosphogluconate
dehydrogenase. These observations suggest that 1) nonenzymatic
glycosylation may play a role in regulating both erythrocyte
metabolism and Hb-O2 affinity in diabetic subjects, and 2)
vitamin B6 therapy may modify nonenzymatic glycosylation of
hemoglobin in this population.
Diabetes and adrenal disease.
Nestler JE; McClanahan MA
Division of Endocrinology and Metabolism, Medical College of
Virginia, Richmond 23298-0111.
Baillieres Clin Endocrinol Metab (England) Oct 1992, 6 (4)
p829-47
Disorders of the adrenal cortex and medulla can result in
glucose intolerance or overt diabetes mellitus. Cushing's
syndrome, characterized by excessive secretion of
glucocorticoids, impairs glucose tolerance primarily by
causing insulin resistance at the post-receptor level. On the
other hand, phaeochromocytoma and hyperaldosteronism, via the
respective actions of catecholamines and hypokalaemia on the
pancreatic beta-cell, impair glucose tolerance primarily by
inhibiting insulin release. The glucose intolerance associated
with these adrenal disorders is usually only mild to moderate
in severity. Marked hyperglycaemia, glycosuria, and polyuria
are uncommon and ketosis is rare. Moreover, the late
complications of diabetes mellitus are distinctly uncommon in
patients with these disorders, and the prognosis for morbidity
and death is usually that of the underlying disease and not
that of diabetes mellitus. The impaired glucose tolerance
induced by all three of these adrenal disorders usually
return.
[Preventive treatment of diabetic microangiopathy:
blocking the pathogenic mechanisms]
Guillausseau PJ
Service de Medecine B, Hopital Lariboisiere, Paris,
France.
Diabete Metab (France) 1994, 20 (2 Pt 2) p219-28
The development of drugs in order to block metabolic
pathway of glucose responsible for diabetic vascular
dysfunction is in progress. Aldose reductase inhibitors
prevent or reduce the different components of vascular
dysfunction, cataract, neuropathy and nephropathy in animal
models of diabetes. Promising results have been observed in
diabetic patients concerning the prevention of neuropathy and
of retinopathy. Larger scale studies with the second
generation compounds are in progress. Glycation inhibitors,
mainly aminoguanidine, have been shown to prevent or reduce
vascular dysfunction and microvascular complications in animal
models. Trials in diabetic patients with aminoguanidine are
just beginning. Anti-oxidant therapy is also at its early
stage of development (vitamin E, vitamin C, alpha lipoic
acid). Antiplatelet agents (aspirin, ticlopidine) have been
demonstrated to reduce the progression of non proliferative
diabetic retinopathy. Angiotensin converting enzyme inhibitors
are of particular interest in preventing diabetic
glomerulopathy. (83 Refs.)
Alternative therapeutic principles in the
prevention of microvascular and neuropathic
complications.
Gries FA
Diabetesforschungsinstitut an der Heinrich-Heine-Universitat,
Dusseldorf, Germany.
Diabetes Res Clin Pract (Ireland) Aug 1995, 28 Suppl
pS201-7
Since the prevention of chronic diabetic complications by
near normal metabolic control is not always achievable,
alternative therapeutic principles have been developed. The
specific intervention at metabolic abnormalities which seem to
play a key role in the pathogenesis of complications has been
shown to prevent the development of microangiopathy and
neuropathy in experimental diabetes, e.g. inhibition of
non-enzymatic glycation by aminoguanidine, inhibition of
polyol pathway activity by aldose reductase inhibitors,
prevention of hypoxia and oxidative stress by vasodilators and
radical scavengers such as alpha-lipoic acid. Some of these
drugs should soon be available for common clinical use. (12
Refs.)
Enhancement of glucose disposal in patients with
type 2 diabetes by alpha-lipoic acid.
Jacob S; Henriksen EJ; Schiemann AL; Simon I; Clancy DE;
Tritschler HJ; Jung WI; Augustin HJ; Dietze GJ
Department of Internal Medicine, City Hospital, Baden-Baden,
Germany.
Arzneimittelforschung (Germany) Aug 1995, 45 (8)
p872-4
Insulin resistance of skeletal muscle glucose uptake is a
prominent feature of Type II diabetes (NIDDM); therefore
pharmacological interventions should aim to improve insulin
sensitivity. Alpha-lipoic acid (CAS 62-46-4, thioctic acid,
ALA), a natural occurring compound frequently used for
treatment of diabetic polyneuropathy, enhances glucose
utilization in various experimental models. To see whether
this compound also augments insulin mediated glucose disposal
in NIDDM, 13 patients received either ALA (1000
mg/Thioctacid/500 ml NaCl, n = 7) or vehicle only (500 ml
NaCl, n = 6) during a glucose-clamp study. Both groups were
comparable in age, body-mass index and duration of diabetes
and had a similar degree of insulin resistance at baseline.
Acute parenteral administration of ALA resulted in a
significant increase of insulin-stimulated glucose disposal;
metabolic clearance rate (MCR) for glucose rose by about 50%
(3.76 ml/kg/min = pre vs. 5.82 ml/kg/min = post, p < 0.05),
whereas the control group did not show any significant change
(3.57 ml/kg/min = pre vs. 3.91 ml/kg/min = post). This is the
first clinical study to show that alpha-lipoic acid increases
insulin stimulated glucose disposal in NIDDM. The mode of
action of ALA and its potential use as an antihyperglycemic
agent require further investigation.
Inhibition with N-acetylcysteine of enhanced
production of tumor necrosis factor in streptozotocin-induced
diabetic rats.
Sagara M; Satoh J; Zhu XP; Takahashi K; Fukuzawa M; Muto G;
Muto Y; Toyota T
Third Department of Internal Medicine, Tohoku University
School of Medicine, Sendai, Japan.
Clin Immunol Immunopathol (United States) Jun 1994, 71 (3)
p333-7
We previously reported that the in vivo production of the
tumor necrosis factor alpha (TNF) was significantly enhanced
after the onset of diabetes in spontaneous type 1 and 2
diabetic animals. In this report we confirmed the enhanced
production of TNF in streptozotocin (STZ)-induced diabetes and
then attempted to suppress the enhanced TNF production with
N-acetylcysteine (NAC), a precursor of glutathione synthesis.
The lipopolysaccharide-induced serum TNF activities were
significantly enhanced in STZ-induced diabetic rats (6-18
weeks of age) compared with those of nondiabetic rats
throughout the 12-week experiment. A single, oral
administration of NAC (200 or 1000 mg/kg body wt)
significantly suppressed the enhanced TNF production in the
diabetic rats compared with that in untreated rats in a
dose-dependent manner. On the other hand, in the long-term (6
or 12 weeks) administrations, smaller doses of NAC (50 or 200
mg/kg/day) also significantly inhibited the enhanced
production of TNF regardless of the dose of NAC. NAC
administration, however, did not suppress the TNF production
of nondiabetic rats. The long-term NAC administration affected
neither body weight nor levels of serum glucose, fructosamine,
albumin, and triglyceride. These results show that NAC
administration significantly suppressed the enhanced TNF
production in diabetic rats and indicate that NAC might be
useful in preventing TNF-mediated pathological conditions in
diabetes.
Effects of acetyl- and proprionyl-L-carnitine on
peripheral nerve function and vascular supply in experimental
diabetes.
Cotter MA; Cameron NE; Keegan A; Dines KC
Department of Biomedical Sciences, University of Aberdeen,
Scotland, UK.
Metabolism (United States) Sep 1995, 44 (9)
p1209-14
L-Carnitine metabolism is abnormal in diabetes mellitus,
and treatment with acetyl-L-carnitine (ALC) improves the
function of cardiac muscle, retina, and peripheral nerve in
experimental models. The aim was to compare the effects of ALC
and proprionyl-L-carnitine (PLC) on motor and sensory nerve
conduction in streptozotocin-diabetic rats and to ascertain
whether their action could be mediated by a vascular
mechanism. ALC and PLC treatment for 2 months after diabetes
induction attenuated the development of sciatic motor nerve
conduction velocity (NCV) deficits by 59.4% +/- 4.4% and 46.9%
+/- 3.2%, respectively. There was a similar level of
protection for sensory saphenous NCV (42.9% +/- 6.6% and 47.8%
+/- 6.0%, respectively). Neither ALC nor PLC prevented the
development of resistance to hypoxic conduction failure (RHCF)
in sciatic nerve from diabetic rats. A 46.5% +/- 3.4% deficit
in sciatic endoneurial blood flow, measured by microelectrode
polarography and hydrogen clearance, in diabetic rats was
partially prevented by both ALC (48.7% +/- 6.4%) and PLC
(69.4% +/- 10.1%). ALC had no significant effect on blood flow
in nondiabetic rats. Thus, the data show that these
L-carnitine derivatives have a similar efficacy in preventing
nerve dysfunction, which depends on a neurovascular
action.
Acetyl-L-carnitine for symptomatic diabetic
neuropathy [letter]
Quatraro A; Roca P; Donzella C; Acampora R; Marfella R;
Giugliano D
Diabetologia (Germany) Jan 1995, 38 (1) p123
No abstract.
Peptide alterations in autonomic diabetic
neuropathy prevented by acetyl-L-carnitine.
Gorio A; Di Giulio AM; Tenconi B; Donadoni L; Germani E;
Bertelli A; Mantegazza P; Maccari F; Ramacci MT
Department of Medical Pharmacology, Faculty of Medicine,
University of Milan, Italy.
Int J Clin Pharmacol Res (Switzerland) 1992, 12 (5-6)
p225-30
Autonomic neuropathy and gastrointestinal problems are
among the most common complications of diabetes. In this
report it is shown that a possible correlation between the two
disorders might exist, since diabetes causes a profound
alteration of the peptidergic innervation of the gut. It is
reported that 14 weeks after diabetes induction with alloxan
the levels of substance P and methionine-enkephalin are
markedly reduced throughout the intestine, while vasoactive
intestinal polypeptide content is dramatically increased.
Therefore the enteric innervation of diabetic animals is
completely disorganized, with some systems undergoing atrophy
and others undergoing hypertrophy. Treatment of diabetic
animals with acetyl-L-carnitine prevents the onset of the
marked peptide changes described above. The results suggest a
potential for acetyl-L-carnitine in the treatment of autonomic
neuropathies.
Prevention of cardiovascular and renal pathology of
aging by the advanced glycation inhibitor
aminoguanidine.
Li YM; Steffes M; Donnelly T; Liu C; Fuh H; Basgen J; Bucala
R; Vlassara H
Picower Institute for Medical Research, Manhasset, NY 11030,
USA.
Proc Natl Acad Sci U S A (United States) Apr 30 1996, 93 (9)
p3902-7
Human aging is impacted severely by cardiovascular disease
and significantly but less overtly by renal dysfunction.
Advanced glycation endproducts (AGEs) have been linked to
tissue damage in diabetes and aging, and the AGE inhibitor
aminoguanidine (AG) has been shown to inhibit renal and
vascular pathology in diabetic animals. In the present study,
the effects of AG on aging-related renal and vascular changes
and AGE accumulation were studied in nondiabetic female
Sprague-Dawley (S-D) and Fischer 344 (F344) rats treated with
AG (0.1% in drinking water) for 18 mo. Significant increases
in the AGE content in aged cardiac (P < 0.05), aortic (P
< 0.005), and renal (P < 0.05) tissues were prevented by
AG treatment (P < 0.05 for each tissue). A marked
age-linked vasodilatory impairment in response to
acetylcholine and nitroglycerine was prevented by AG treatment
(P < 0.005), as was an age-related cardiac hypertrophy
evident in both strains (P < 0.05). While creatinine
clearance was unaffected by aging in these studies, the AGE/
creatinine clearance ratio declined 3-fold in old rats vs.
young rats (S-D, P < 0.05; F344, P < 0.01), while it
declined significantly less in AG-treated old rats (P <
0.05). In S-D but not in F344 rats, a significant (P <
0.05) age-linked 24% nephron loss was completely prevented by
AG treatment, and glomerular sclerosis was markedly suppressed
(P < 0.01). Age-related albuminuria and proteinuria were
markedly inhibited by AG in both strains (S-D, P < 0.01;
F344, P < 0.01). These data suggest that early interference
with AGE accumulation by AG treatment may impart significant
protection against the progressive cardiovascular and renal
decline afflicting the last decades of life.
Prevention of long-term complications of
non-insulin-dependent diabetes mellitus.
Nathan DM
Harvard Medical School, Diabetes Clinic, Massachusetts
General Hospital, Boston, Mass., USA
Clin Invest Med (Canada) Aug 1995, 18 (4) p332-9
Non-insulin-dependent diabetes mellitus (NIDDM) may be the
most rapidly-growing chronic disease in the world. Its
long-term complications, including retinopathy, nephropathy,
neuropathy, and accelerated macrovascular disease cause major
morbidity and mortality. Although therapy that normalizes
glycemia may prevent the development and delay the progression
of long-term complications in NIDDM, as has been demonstrated
in insulin-dependent diabetes mellitus (IDDM), no direct data
exist to support the efficacy of "intensive therapy" in NIDDM.
An alternative approach to preventing the development of
long-term complications may be to intervene more distally,
i.e., inhibit the mechanism(s) by which elevated glucose
levels cause complications. Potential pathogenic mechanisms
include the accumulation of sorbitol and other biochemical
changes in tissues with aldose reductase, and the modification
of proteins by glycation. Pharmacologic probes, including
aldose reductase inhibitors and glycation inhibitors such as
aminoguanidine, are currently under study and may provide an
efficient means of preventing complications, independent of
the ambient glycemic level. (44 Refs.)
Secondary intervention with aminoguanidine retards
the progression of diabetic retinopathy in the rat
model.
Hammes HP; Strodter D; Weiss A; Bretzel RG; Federlin K;
Brownlee M
Third Medical Department, Justus-Liebig-University, Giessen,
Germany.
Diabetologia (Germany) Jun 1995, 38 (6) p656-60
Primary prevention with aminoguanidine-an inhibitor of
advanced glycation end product (AGE) formation--has been
successfully employed to prevent diabetic retinopathy in the
rat. However, it is unknown whether inhibition of AGE
formation is still effective in a secondary intervention
strategy. The present study addresses this question by
comparing secondary intervention with aminoguanidine with
syngeneic islet transplantation in the rat model. After 6
months of diabetes, one group was treated with aminoguanidine
(50 mg/100 ml drinking water; D-AG) while another group
received syngeneic transplantation of collagenase-ficoll
isolated islets by intraportal injection (Tx). After an
additional 4 months, both groups were compared to a normal (NC
10) and diabetic (DC 10) control group. Retinal
autofluorescence was increased 2.5-fold after 6 months and
increased 3.7-fold after 10 months of diabetes (p < 0.001).
Aminoguanidine and islet Tx retarded the further accumulation
of autofluorescence equally (p < 0.001 vs DC 10), although
the values were higher than those observed in DC at 6 months
(p < 0.001). Diabetes was associated with a 2.7-fold
increase in acellular capillaries after 6 months and a
4.1-fold increase after 10 months. Treatment with
aminoguanidine or islet Tx reduced but did not completely
attenuate the progression of vascular occlusion (p < 0.001
vs DC 10; D-AG vs DC 6, p < 0.05; Tx vs DC 6, p < 0.01).
Both treatments reduced endothelial proliferation (22.4% after
10 months; p < 0.001) and completely arrested pericyte
dropout (40% after 10 months; p < 0.001).
Prevention of glomerular basement membrane
thickening by aminoguanidine in experimental diabetes
mellitus.
Ellis EN; Good BH
Department of Pediatrics, University of Arkansas for Medical
Science, Little Rock.
Metabolism (United States) Oct 1991, 40 (10)
p1016-9
The etiology of diabetic glomerulopathy appears to be
related, at least in part, to the degree of hyperglycemia, the
resultant nonenzymatic glycosylation of proteins, and the
eventual formation of advanced glycosylation end products in
long-lived structural proteins. To investigate the
relationship between the glomerular basement membrane (GBM)
changes of diabetic nephropathy and the formation of advanced
glycosylation end products, we studied control rats, diabetic
rats, and control and diabetic rats who received
aminoguanidine, a compound that pharmacologically inhibits
formation of advanced glycosylation end products. After 9
months, rat weight was smaller and kidney weight larger in
both diabetic groups compared with both control groups. GBM
width was increased in the diabetic group compared with the
control group. Aminoguanidine administration to diabetic rats
ameliorated this increase in GBM. Thus, aminoguanidine
administration from the onset of experimental diabetes
prevented the widening of the GBM that is typical of
diabetes.
Can metformin reduce insulin resistance in
polycystic ovary syndrome?
Acbay O; Gundogdu S
Department of Internal Medicine, Cerrahpasa Medical Faculty
of Istanbul University, Turkey.
Fertil Steril (United States) May 1996, 65 (5)
p946-9
OBJECTIVE: To examine whether metformin is able to reduce
insulin resistance in polycystic ovary syndrome (PCOS).
DESIGN: Single-blind study comprising two successive
periods of treatment: 8 weeks of placebo and 10 weeks of
metformin (orally, 850 mg twice daily).
SETTING: Clinic of endocrinology and metabolism of
Cerrahpasa Medical Faculty at Istanbul University, Istanbul,
Turkey.
PATIENTS: Sixteen insulin-resistant women with PCOS.
INTERVENTIONS: Insulin sensitivity (with an IV insulin
tolerance test), plasma glucose and insulin levels during an
oral glucose tolerance test (OGTT), serum androgens, and
lipids were measured at baseline and after each treatment
period.
RESULTS: Insulin sensitivity, the mean fasting serum levels
of glucose, insulin, total cholesterol, triglyceride,
low-density lipoprotein cholesterol, high-density lipoprotein
cholesterol, total T, free T, androstenedione, DHEAS, and
LH:FSH ratio, and the areas under the curve for plasma glucose
and insulin during OGTT were not changed.
Effects of diet and metformin administration on sex
hormone-binding globulin, androgens, and insulin in hirsute
and obese women.
Crave JC; Fimbel S; Lejeune H; Cugnardey N; Dechaud H; Pugeat
M
Hospices Civils de Lyon, Laboratoire de la Clinique
Endocrinologique, Hopital de l'Antiquaille, France.
J Clin Endocrinol Metab (United States) Jul 1995, 80 (7)
p2057-62
Evidence suggests that hyperinsulinemic insulin resistance
may increase serum levels of ovarian androgens and reduce sex
hormone-binding globulin (SHBG) levels in humans. The present
study was conducted to assess the effect of administration of
the biguanide metformin, a drug commonly used in the treatment
of diabetes mellitus, on androgen and insulin levels in 24
hirsute patients. The patients selected for the study were
obese, with a body mass index higher than 25 kg/m2 and high
fasting insulin (> 90 pmol/L) and low SHBG levels (< 30
nmol/L). All patients were given a low calorie diet (1500
Cal/day) and randomized for either metformin administration at
a dose of 850 mg or a placebo, twice daily for 4 months, in a
double blind study. In the placebo group, diet resulted in a
significant decrease in body mass index (30.8 +/- 1.0 vs. 32.7
+/- 1.5 kg/m2; P < 0.0001), fasting insulin (127 +/- 11 vs.
156 +/- 14 pmol/L; P < 0.01), non-SHBG-bound testosterone
(0.19 +/- 0.02 vs. 0.28 +/- 0.03 nmol/L; P < 0.02),
androstenedione (5.8 +/- 0.5 vs. 9.0 +/- 1.1 nmol/L; P <
0.03), and 3 alpha-diolglucuronide (8.6 +/- 1.1 vs. 11.7 +/-
1.9; P < 0.005) plasma concentrations and a significant
increase in the glucose/insulin ratio (0.047 +/- 0.005 vs.
0.035 +/- 0.003; P < 0.001) and plasma concentrations of
SHBG (26.0 +/- 3.3 vs. 19.1 +/- 1.9 nmol/L; P < 0.001) and
dehydroepiandrosterone sulfate (8.7 +/- 1.5 vs. 8.4 +/- 1.3; P
< 0.05). Beneficial effects of diet were not significantly
different in the patients who were given metformin instead of
placebo. These results confirm that weight loss induced by a
low calorie diet is effective in improving hyperinsulinemia
and hyperandrogenism in obese and hirsute women. With our
study design, metformin administration had no additional
benefit over the effect of diet.
[The value of metformin in therapy of type 2
diabetes: effect on insulin resistance, diabetic control and
cardiovascular risk factors]
Schernthaner G
Medizinische Abteilung, Krankenanstalt Rudolfstiftung,
Wien.
Wien Klin Wochenschr (Austria) 1994, 106 (24)
p793-802
In this review article recently published controlled
clinical studies of metformin treatment in type-2 diabetic
patients are summarized. Several studies demonstrate that body
weight decreases and insulin resistance improves--as evaluated
by peripheral glucose utilisation--under metformin treatment.
HbA1c is lowered by approximately 20% (absolute decrease of
HbA1c: 1.0%-1.5%). Since plasma lipid values and
plasminogen-activator-inhibitor (PAI-1) concentrations are
also lowered under metformin therapy, it currently represents
the treatment of choice for the obese group of type-2 diabetic
patients. (104 Refs.)
Oral vanadyl sulfate improves hepatic and
peripheral insulin sensitivity in patients with
non-insulin-dependent diabetes mellitus.
Cohen N; Halberstam M; Shlimovich P; Chang CJ; Shamoon H;
Rossetti L
Department of Medicine, Albert Einstein College of Medicine,
New York 10461, USA.
J Clin Invest (United States) Jun 1995, 95 (6)
p2501-9
We examined the in vivo metabolic effects of vanadyl
sulfate (VS) in non-insulin-dependent diabetes mellitus
(NIDDM). Six NIDDM subjects treated with diet and/or
sulfonylureas were examined at the end of three consecutive
periods: placebo for 2 wk, VS (100 mg/d) for 3 wk, and placebo
for 2 wk. Euglycemic hyperinsulinemic (30 mU/m2.min) clamps
and oral glucose tolerance tests were performed at the end of
each study period. Glycemic control at baseline was poor
(fasting plasma glucose 210 +/- 19 mg/dl; HbA1c 9.6 +/- 0.6%)
and improved after treatment (181 +/- 14 mg/dl [P < 0.05],
8.8 +/- 0.6%, [P < 0.002]); fasting and post-glucose
tolerance test plasma insulin concentrations were unchanged.
After VS, the glucose infusion rate during the clamp was
increased (by approximately 88%, from 1.80 to 3.38 mg/kg.min,
P < 0.0001). This improvement was due to both enhanced
insulin-mediated stimulation of glucose uptake (rate of
glucose disposal [Rd], +0.89 mg/kg.min) and increased
inhibition of HGP (-0.74 mg/kg.min) (P < 0.0001 for both).
Increased insulin-stimulated glycogen synthesis (+0.74
mg/kg.min, P < 0.0003) accounted for > 80% of the
increased Rd after VS, and the improvement in insulin
sensitivity was maintained after the second placebo period.
The Km of skeletal muscle glycogen synthase was lowered by
approximately 30% after VS treatment (P < 0.05). These
results indicate that 3 wk of treatment with VS improves
hepatic and peripheral insulin sensitivity in
insulin-resistant NIDDM humans. These effects were sustained
for up to 2 wk after discontinuation of VS.
Toxicity studies on one-year treatment of
non-diabetic and streptozotocin-diabetic rats with vanadyl
sulphate.
Dai S; Thompson KH; Vera E; McNeill JH
Division of Pharmacology and Toxicology, Faculty of
Pharmaceutical Sciences, University of British Columbia,
Vancouver, Canada.
Pharmacol Toxicol (Denmark) Nov 1994, 75 (5)
p265-73
Streptozotocin-diabetic and non-diabetic rats were given
vanadyl sulphate in drinking water at concentrations of
0.5-1.5 mg/ml for one year. It was found that vanadyl
treatment did not produce persistent changes in plasma
aspartate aminotransferase, alanine aminotransferase, and
urea, specific morphological abnormalities in the brain,
thymus, heart, lung, liver, spleen, pancreas, kidney, adrenal,
or testis, or abnormal organ weight/body weight ratio for
these organs in either non-diabetic or diabetic animals.
Treatment significantly reduced the incidence of the
occurrence of urinary stones in non-diabetic rats. In diabetic
animals vanadyl treatment significantly reduced the mortality
rate and prevented the elevation of plasma levels of alanine
aminotransferase and urea, the increases in organ size, and
the occurrence of megacolon but did not affect the development
of renal and testicular tumours. Plasma and tissue
concentrations of vanadium were determined and found to have
the following order of distribution: bone > kidney >
testis > liver > pancreas > plasma > brain.
Vanadium was retained in these organs at 16 weeks following
vanadyl withdrawal while the plasma levels were beneath
detection limits. It is concluded that vanadyl sulphate at
antidiabetic doses is not significantly toxic to rats
following a one-year administration in drinking water, but
vanadium may be retained in various organs for months after
cessation of treatment.
Antidiabetic action of vanadyl in rats independent
of in vivo insulin-receptor kinase activity.
[No author listed]
Diabetes (United States) Apr 1991, 40 (4) p492-8
The effects of oral vanadyl sulfate administration for 9-12
days on carbohydrate and lipid metabolism in the basal state
and on glucose dynamics during submaximal hyperinsulinemic
clamps were investigated in nondiabetic and
streptozocin-induced diabetic rats. Decreases in growth rate
and water and food consumption were the only significant
alterations noted in control animals receiving vanadyl.
Administration of vanadyl to diabetic rats resulted in weight
loss; a significant decrease in plasma glucose, triglyceride,
and cholesterol levels; and decreases in food and water
intake, without a concomitant change in plasma insulin
concentrations. Vanadyl treatment did not modify either
peripheral glucose utilization or hepatic glucose production
in control rats during submaximal insulin clamps. In contrast,
vanadyl therapy increased insulin-induced glucose utilization
significantly and had a small but nonsignificant effect on
insulin-mediated suppression of glucose production in diabetic
rats. The tyrosine kinase activity of liver- and
muscle-derived insulin receptors from diabetic rats that
underwent clamp study, which reflected the in vivo
phosphorylation state of insulin receptor, was not altered by
vanadyl treatment. In conclusion, these results show that
augmentation of peripheral glucose utilization is the major
determinant of the antidiabetic action of vanadyl and support
the notion that the action of vanadyl is independent of
insulin-receptor kinase activity.
A high biotin diet improves the impaired glucose
tolerance of long-term spontaneously hyperglycemic rats with
non-insulin-dependent diabetes mellitus
Zhang H.; Osada K.; Maebashi M.; Ito M.; Komai M.; Furukawa
Y.
H. Zhang, Laboratory of Nutrition, Dept. Applied Biological
Chemistry, Faculty of Agriculture, Sendai 981 Japan
Journal of Nutritional Science and Vitaminology (Japan),
1996, 42/6 (517-526)
The Otsuka Long-Evans Tokushima Fatty (OLETF) rat, serving
as a spontaneously diabetic model with non-insulin-dependent
diabetes mellitus (NIDDM),exhibits impaired glucose tolerance
(IGT) at about 16 weeks of age. In this study, we investigated
whether or not biotin, a water-soluble vitamin, improved the
IGT of OLETF rats. To this end, we administered diets
containing one of three levels of biotin, a high-biotin diet
(BH), a normal-biotin diet (BN) and a basal-biotin diet (BB),
to OLETF rats up to 24 weeks of age. An oral glucose tolerance
test (OGTT) was performed four times between 13 and 22 weeks
of age. The administration of a BH corrected the IGT of OLETF
rats. Upon further investigation, we found that insulin
secretion in the OLETF-BH rats was decreased to a significant
extent, signaling that the hyperinsulinemia typical to the
OLETF-BH rats had clearly improved. Body weights were
significantly lower in the OLETF-BH group than in the other
OLETF groups, even though the OLETF-BH rats showed a
significantly higher average daily food intake. The body
weight gain of the OLETF-BH rats followed the same tendency as
the control-LETO (Long Evans Tokushima Otsuka) rats (LETO-BB
and LETO-BN). These results demonstrate that a high-level
biotin diet can improve the glucose handicap in NIDDM
rats.
Oral glucose tolerance test after high-dose i.v.
biotin administration in normoglucemic hemodialysis
patients
Koutsikos D.; Fourtounas C.; Kapetanaki A.; Agroyannis B.;
Tzanatos H.; Rammos G.; Kopelias I.; Bosiolis B.; Bovoleti O.;
Darema M.; Sallum G.
Aretaieon University Hospital, 76, Vas. Sofias AVE, 115 28
Athens Greece
Renal Failure (USA), 1996, 18/1 (131-137)
Abnormal glucose metabolism in uremia may result from a
complex interplay between decreased insulin secretion and
insulin resistance. Recent studies report beneficial effect of
biotin administration in glucose metabolism in diabetic
animals and in a small number of patients with diabetes
mellitus. The aim of the present study was to evaluate the
response of oral glucose tolerance test (OGTT) to the i.v.
administration of large doses of biotin in hemodialysis
patients. Eleven hemodialysis patients aged 56.90 plus or
minus 11.20 (32- 76) years on regular hemodialysis thrice a
week for 2.72 plus or minus 1.79 (1-7) years were studied.
Fasting venous plasma glucose, glucosylated hemoglobin (%GH),
and plasma glucose concentration 2 h after the administration
of a 75-g glucose load were measured before, and 2 weeks and 2
months after administration of 50 mg of biotin i.v.
postdialysis, and after a 2-month washout period. During the
study, dialysis schedule and patients' medication, diet, and
dry weight were kept unchanged. OGTT was abnormal in 4
patients before biotin administration and became normal in 3
patients (75%). Our results offer support to the findings of
other studies about the beneficial effect of biotin in
experimental or clinical diabetes mellitus, and argue for the
involvement of biotin in glucose metabolism.
Transcriptional regulation of liver
phosphoenolpyruvate carboxykinase by biotin in diabetic
rats
Dakshinamurti K.; Li W.
Biochemistry/Molecular Biology Dept., University of Manitoba,
Winnipeg, Man. R3E OW3 Canada
Mol Cell Biochem 1994 Mar 30;132(2):127-32
Rat liver phosphoenolpyruvate carboxykinase (PEPCK)
activity was followed over a time period of 5 h following
administration of biotin to streptozotocin-induced diabetic
rats. In parallel with the decrease in enzyme activity liver
PEPCK mRNA decreased by 85% at 3 h after injection of biotin
to diabetic rats. There was no significant change in the
accumulation of kidney PEPCK mRNA. Parallel studies with
insulin indicated that biotin had a regulatory effect similar
to that of insulin on liver PEPCK mRNA. The administration of
biotin did not change the insulin status of the diabetic rat
indicating that biotin did not act via insulin. The
transcriptional activity of the hepatic PEPCK gene, as
measured by nuclear run-on assay; was decreased by 57% within
30 min of biotin administration. The results suggest that
biotin regulates hepatic, but not renal, PEPCK mRNA
concentration at the transcriptional level in diabetic
rats.
Effect of biotin on the regulation of glucokinase
in the intact rat
Hsieh Y.T.L.; Mistry S.P.
Department of Poultry/Avian Sciences, Institute of Food
Science, Cornell University, Ithaca, NY 14853-5601 USA
Nutr. Res. (USA), 1992, 12/6 (787-799)
Glucokinase activity was affected by hormones, dietary
state, and dietary sources (e.g., glucose). Therefore, various
factors (such as glucose, insulin, and biotin) affecting
glucokinase activity in the rat liver were investigated. The
activity of glucokinase was low in diabetic, fasting, and/or
biotin-deficient rats. In the present study, the de novo
synthesis of the glucokinase induced by the insulin and biotin
in the intact rat was proposed. The first induction of
glucokinase was activated by insulin. The second phase of
enzyme activity could be induced by biotin. In addition,
supplementation of cGMP with glucose and insulin to biotin
deficient rats fully restored the enzyme activity as did
biotin, showing that cGMP induction of glucokinase was
dependent on the biotin status of the animal.
Biotin supplementation improves glucose and insulin
tolerances in genetically diabetic KK mice
Reddi A.; DeAngelis B.; Frank O.; Lasker N.; Baker H.
Department of Medicine, Division of Nephrology, University of
Medicine and Dentistry of New Jersey-New Jersey Medical
School, Newark, NJ 07107-3006 USA
Life Sci 1988;42(13):1323-30
Because biotin treatment may lower blood glucose in
insulin-dependent diabetes, we chose to study such an effect
in non-insulin dependent diabetes. Twenty-six diabetic KK
mice, moderately hyperglycemic and insulin resistant, were
treated for 10 weeks: 9 animals with 2 mg of biotin/Kg, 8 with
4 mg of biotin/Kg, and 9 with saline (controls). Blood glucose
levels, oral glucose tolerance, insulin response to oral
glucose, and blood glucose decrease in response to insulin
were quantitated. Compared to controls, biotin treatment
lowered post-prandial glucose levels, and improved tolerance
to glucose and insulin resistance. Serum immunoreactive
insulin levels in biotin-treated mice were like the
controls.
Biotin administration improves the impaired glucose
tolerance of streptozotocin-induced diabetic Wistar
rats.
Zhang H, Osada K, Sone H, Furukawa Y
Department of Applied Biological Chemistry, Faculty of
Agriculture Tohoku University Sendai Japan.
J Nutr Sci Vitaminol (Tokyo) 1997
Jun;43(3):271-80
The effect of biotin administration on the glucose
tolerance of streptozotocin (STZ)-induced diabetic Wistar rats
was investigated. STZ-induced diabetes was induced by
intraperitoneal injection of streptozotocin (45 mg/kg body
weight as a single dose). The impaired glucose tolerance in
response to an oral glucose load (1.8g per kg body weight) in
STZ-induced diabetic rats (STZ-rat) was partially improved by
intraperitoneal administration of biotin for 15 days (100
micrograms/rat/day). However, a recovery in the STZ-rat's
insulin secretion was not found after biotin administration.
To help clarify the mechanism underlying the improvement in
glucose tolerance seen with biotin treatment, glucokinase and
hexokinase activities were determined in the liver and
pancreas. In STZ-rats that had received biotin (STZ-biotin
rats), glucokinase activity was higher by 3.4-fold in liver
and by 2.4-fold in pancreas than in the STZ-rats. The biotin
level of STZ-rats was significantly lower in the liver and
pancreas than that of the control rats (no STZ
administration); but in STZ-biotin rats, the level in these
organs recovered to the control level. These results
demonstrate that injected biotin can improve glucose handling
without increasing insulin secretion in STZ-rats.
Biotin for diabetic peripheral neuropathy.
Koutsikos D, Agroyannis B, Tzanatos-Exarchou H
University of Athens, Aretaieon University Hospital
Greece.
Biomed Pharmacother 1990;44(10):511-4
Biotin in high doses was given for 1-2 years to three
diabetic patients suffering from severe diabetic peripheral
neuropathy. Within 4-8 weeks there was a marked improvement in
clinical and laboratory findings. It is suggested that in
diabetes may exist a deficiency, inactivity or unavailability
of Biotin, resulting in disordered activity of
biotin-dependent enzyme, pyruvate carboxylase, leading to
accumulation of pyruvate and/or depletion of aspartate, both
of which play a significant role in nervous system metabolism.
Based on our good results, regular biotin administration could
be suggested for every diabetic patient for the prevention and
management of peripheral neuropathy although extensive
randomised clinical trials are required.
Tissue concentrations of water-soluble vitamins in
normal and diabetic rats.
Reddi AS, Jyothirmayi GN, DeAngelis B, Frank O, Baker H
Department of Medicine, UMDNJ-New Jersey Medical School
Newark 07103.
Int J Vitam Nutr Res 1993;63(2):140-4
Changes in circulating and tissue concentrations of several
vitamins have been reported in diabetic animals and human
subjects. In this study, the effect of short-term (2 weeks)
streptozotocin diabetes on folate, B6, B12, thiamin,
nicotinate, pantothenate, riboflavin and biotin in liver,
kidney, pancreas, heart, brain and skeletal muscle of rats was
investigated. The tissue distribution of vitamins varied
widely in normal rats. Diabetes significantly lowered folate
in kidney, heart, brain, and muscle; B6 in brain; B12 in
heart; thiamin in liver and heart; nicotinate in liver,
kidney, heart and brain; pantothenate in all tissues;
riboflavin in liver, kidney, heart, and muscle. These results
indicate that experimental diabetes causes a depression of
several water-soluble vitamins in various tissues of rats.
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