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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