1_ [Enhancement of glucoseinduced insulin secretion and modification
of
glucose metabolism by biotin]
Furukawa Y
Division of Life Science, Graduate School of Agricultural Science, Tohoku
University. Nippon rinsho (JAPAN) Oct 1999, 57 (10) p22619
Biotin causes improvements in disordered glucose metabolism by
stimulating glucoseinduced insulin secretion in pancreatic betacells and
by accelerating glycolysis in liver and pancreas. Biotin is known to
regulate hepatic and pancreatic glucokinase expression at both
transcriptional and translational levels, and to regulate hepatic
phosphoenolpyruvate carboxykinase expression at the transcriptional level.
The effects of biotin on glucoseinduced insulin secretion were
investigated using the method of isolated pancreas perfusion. The pancreas
of the biotindeficient rat has an impaired insulin response to both
glucose and arginine. In control rats as well as biotindeficient rats,
the
insulin response to glucose stimulation was enhanced by the addition of
1
mM biotin to the perfusate. Biotininduced enhancement of glucoseinduced
insulin release was evident within the first few minutes of perfusion.
Since any effects on the glucokinase synthesis pathway would not be seen
for at least 30 minutes, these results indicate that biotin may have the
ability to act directly on the insulin secreting function of pancreatic
betacells. Biotin perfusion was not found to cause enhancement of the
arginineinduced insulin response, suggesting that biotin has no
significant effects on the distal portion of the signaling pathway involved
in insulin secretion. These results indicate that the administration of
a
high concentrations of biotin may improve the metabolism and/or utilization
of glucose in patients with noninsulindependent diabetes mellitus. (22
Refs.)
2_ A high biotin diet improves the impaired glucose tolerance of longterm
spontaneously hyperglycemic rats with noninsulindependent 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 (517526)
The Otsuka LongEvans Tokushima Fatty (OLETF) rat, serving as a spontaneously
diabetic model with noninsulindependent diabetes mellitus (NIDDM),exhibits
impaired glucose tolerance (IGT) at about 16 weeks of age. In this study,
we investigated whether or not biotin, a watersoluble vitamin, improved
the IGT of OLETF rats. To this end, we administered diets containing one
of three levels of biotin, a highbiotin diet (BH), a normalbiotin diet
(BN) and a basalbiotin 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 OLETFBH rats was decreased to a significant extent, signaling that
the hyperinsulinemia typical to the OLETFBH rats had clearly improved.
Body weights were significantly lower in the OLETFBH group than in the
other OLETF groups, even though the OLETFBH rats showed a significantly
higher average daily food intake. The body weight gain of the OLETFBH
rats followed the same tendency as the controlLETO (Long Evans Tokushima
Otsuka) rats (LETOBB and LETOBN). These results demonstrate that a highlevel
biotin diet can improve the glucose handicap in NIDDM rats.
3_ Oral glucose tolerance test after highdose 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 (131137)
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 (17) years were studied. Fasting venous plasma
glucose, glucosylated hemoglobin (%GH), and plasma glucose concentration
2 h after the administration of a 75g glucose load were measured before,
and 2 weeks and 2 months after administration of 50 mg of biotin i.v.
postdialysis, and after a 2month 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.
4_ Oral glucose tolerance test after highdose 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
Department of Nephrology, Aretaieon University Hospital, Athens, Greece.
Renal Failure (USA) , 1996, 18/1 (131137)
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 +/ 11.20
(3276) years on regular hemodialysis thrice a week for 2.72 +/ 1.79 (17)
years were studied. Fasting venous plasma glucose, glucosylated hemoglobin
(%GH), and plasma glucose concentration 2 h after the administration of
a 75g 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.
5_ Helicon Foundation, San Diego, CA, USA. Med Hypotheses 2000 Mar;54(3):4837
It may now be feasible to target specific supplemental nutrients to each
of the key dysfunctions which conspire to maintain hyperglycemia in type
2 diabetes: bioactive chromium for skeletal muscle insulin resistance,
conjugated linoleic acid for adipocyte insulin resistance, highdose biotin
for excessive hepatic glucose output, and coenzyme Q(10) for beta cell
failure. Nutritional strategies which disinhibit hepatic fatty acid oxidation
(involving hydroxycitrate, carnitine, pyruvate, and other adjuvants) may
likewise prove beneficial in the short term, by decreasing serum free
fatty acids and, in the longer term, by promoting regression of visceral
obesity. The nutrients and food factors recommended here appear to be
safe and well tolerated, and thus may have particular utility for diabetes
prevention.
6_ Biotin regulation of pancreatic glucokinase and insulin in primary
cultured rat islets and in biotindeficient rats.
RomeroNavarro G; CabreraValladares G; German MS; Matschinsky FM;
Velazquez A; Wang J; FernandezMejia C
Nutritional Genetics Unit, Biomedical Research Institute, National
University of Mexico, Mexico City.
Endocrinology (UNITED STATES) Oct 1999, 140 (10) p4595600
Biotin has been reported to affect glucose homeostasis; however, its
role
on pancreatic islets of Langerhans has not been assessed. In this report,
we demonstrate that physiologic concentrations of biotin stimulate
glucokinase activity in rat islets in culture. Using the branched DNA
(bDNA) assay, a sensitive signal amplification technique, we detected
relative increases in glucokinase mRNA levels of 41.5 +/ 13% and 81.3
+/
19% at 12 and 24 h respectively in islets treated with [10(6) M] biotin.
Because glucokinase activity controls insulin secretion, we also
investigated the effect of biotin on insulin release. Treatment with
[10(6) M] biotin for 24 h increased insulin secretion. We extended our
studies by analyzing the effect of biotin deficiency on pancreatic islet
glucokinase expression and activity, as well as insulin secretion. Our
results show that islet glucokinase activity and mRNA are reduced by 50%
in
the biotin deficient rat. Insulin secretion in response to glucose was
also
impaired in islets isolated from the deficient rat. These data show that
biotin affects pancreatic islet glucokinase activity and expression and
insulin secretion in cultured islets.
7_ Highdose biotin, an inducer of glucokinase expression, may synergize
with chromium picolinate to enable a definitive nutritional therapy for
type II diabetes.
McCarty MF
NutriGuard Research, Encinitas, CA 92024, USA.
Medical hypotheses (ENGLAND) May 1999, 52 (5) p4016
Glucokinase (GK), expressed in hepatocyte and pancreatic beta cells,
has
a central regulatory role in glucose metabolism. Efficient GK activity
is
required for normal glucosestimulated insulin secretion, postprandial
hepatic glucose uptake, and the appropriate suppression of hepatic glucose
output and gluconeogenesis by elevated plasma glucose. Hepatic GK activity
is subnormal in diabetes, and GK may also be decreased in the beta cells
of
type II diabetics. In supraphysiological concentrations, biotin promotes
the transcription and translation of the GK gene in hepatocytes; this
effect appears to be mediated by activation of soluble guanylate cyclase.
More recent evidence indicates that biotin likewise increases GK activity
in islet cells. On the other hand, highdose biotin suppresses hepatocyte
transcription of phosphoenolpyruvate carboxykinase, the ratelimiting
enzyme for gluconeogenesis. Administration of highdose biotin has improved
glycemic control in several diabetic animals models, and a recent Japanese
clinical study concludes that biotin (3 mg t.i.d. orally) can substantially
lower fasting glucose in type II diabetics, without sideeffects. The
recently demonstrated utility of chromium picolinate in type II diabetes
appears to reflect improved peripheral insulin sensitivitya parameter
which is unlikely to be directly influenced by biotin. Thus, the joint
administration of supranutritional doses of biotin and chromium picolinate
is likely to combat insulin resistance, improve betacell function, enhance
postprandial glucose uptake by both liver and skeletal muscle, and inhibit
excessive hepatic glucose production. Conceivably, this safe, convenient,
nutritional regimen will constitute a definitive therapy for many type
II
diabetics, and may likewise be useful in the prevention and management
of
gestational diabetes. Biotin should also aid glycemic control in type
I
patients. (75 Refs.)
8_ Biotin administration improves the impaired glucose tolerance of
streptozotocininduced diabetic Wistar rats.
Zhang H; Osada K; Sone H; Furukawa Y
Department of Applied Biological Chemistry, Faculty of Agriculture,
Tohoku University, Sendai Japan.
Journal of nutritional science and vitaminology (JAPAN) Jun 1997, 43
(3) p27180
The effect of biotin administration on the glucose tolerance of
streptozotocin (STZ)induced diabetic Wistar rats was investigated.
STZinduced 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 STZinduced diabetic rats (STZrat) was partially improved by
intraperitoneal administration of biotin for 15 days (100
micrograms/rat/day). However, a recovery in the STZrat'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 STZrats that had received biotin (STZbiotin rats),
glucokinase activity was higher by 3.4fold in liver and by 2.4fold in
pancreas than in the STZrats. The biotin level of STZrats was
significantly lower in the liver and pancreas than that of the control
rats
(no STZ administration); but in STZbiotin 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
STZrats.
9_ Effect of biotin on glucokinase activity, mRNA expression and insulin
release in cultured betacells.
Borboni P; Magnaterra R; Rabini RA; Staffolani R; Porzio O; Sesti G;
Fusco A; Mazzanti L; Lauro R; Marlier LN
Department of Internal Medicine, University of Rome Tor Vergata, Italy.
Acta diabetologica (GERMANY) Jul 1996, 33 (2) p1548
Biotin is known to influence hepatic glucokinase (GK) expression both
at
a transcriptional and at a translational level. The aim of the present
paper was to investigate the effect of biotin on pancreatic GK. For this
purpose, RIN104638 cells were cultured in the presence of different biotin
concentrations for different times; thereafter, GK mRNA expression, GK
activity and insulin release were studied. Results demonstrated that biotin
has a biphasic effect on GK mRNA expression, being stimulatory after
shortterm treatment and inhibitory after longterm treatment. GK activity
was increased after longterm treatment. Insulin release was not affected
by biotin treatment. These data suggest that biotin may influence glucose
metabolism also by acting directly at the level of betacells.
10_ Transcriptional regulation of the glucokinase gene by biotin in starved
rats.
Chauhan J; Dakshinamurti K
Department of Biochemistry and Molecular Biology, University of Manitoba,
Winnipeg, Canada.
Journal of biological chemistry (UNITED STATES) Jun 5 1991, 266 (16)
p100358
The purpose of this work was to investigate whether biotin, a
watersoluble vitamin, regulates the glucokinase gene. Biotin was
administered intraperitoneally to starved rats, and the time course of
glucokinase induction was followed over a time period of 12 h. The
glucokinase mRNA was increased 19.6fold during the first 1 h after biotin
administration, afterwards rapidly decayed, and was hardly detectable
by 4
h. The amount of glucokinase activity as determined by conventional enzyme
activity assay increased in a timedependent fashion, reaching 4fold by
2
h of biotin administration. The transcriptional activity of the gene as
measured by a nuclear runon assay was increased about 6.7fold within 45
min of biotin administration. These findings indicate that biotin can
regulate the glucokinase gene at the transcriptional stage in the starved
rat.
11_ Effects of biotin upon the intracellular level of cGMP and the activity
of glucokinase in cultured rat hepatocytes.
Spence JT; Koudelka AP
Journal of biological chemistry (UNITED STATES) May 25 1984, 259 (10)
p63936
The effects of biotin upon the intracellular level of cGMP and the
activity of glucokinase were examined in primary cultures of adult rat
hepatocytes. The addition of biotin to the culture medium of hepatocytes
increased their content of cGMP 3fold within 1 h. A 4fold increase in
the
activity of glucokinase was observed in response to the addition of the
vitamin to the culture medium and the maximal response was observed 6
h
following the addition to the medium. These maximum effects were noted
when
biotin was present in the culture medium at a concentration of 10(6) M.
The induction of glucokinase activity by biotin was preceded by an increase
in the intracellular level of cGMP. The addition of 8bromocGMP to the
culture medium also increased the activity of glucokinase and its effects
were not additive with respect to the effects of biotin. The induction
of
glucokinase by biotin or the cyclic nucleotide analog was not observed
in
the absence of insulin. The effects of biotin upon the activity of
glucokinase could be mimicked by including glucose in the culture medium.
When hexose utilization by the hepatocytes was blocked by the addition
to
the culture medium of Nacetylglucosamine, the induction of glucokinase
by
biotin was unaffected, whereas the induction brought about by glucose
was
not observed. The changes in the activity of the enzyme brought about
by
biotin or 8bromocGMP was shown to arise as the result of changes in the
rate of synthesis of the enzyme. In addition, using an in vitro translation
assay and immunoprecipitation, it was found that biotin and 8bromocGMP
increased the amount of translatable mRNA coding for the enzyme.
12_ Towards practical prevention of type 2 diabetes
McCarty M.F.
M.F. McCarty, Pantox Laboratories, 4622 Santa Fe Street, San Diego, CA
92109 United States
Medical Hypotheses ( MED. HYPOTHESES ) (United Kingdom) 2000, 54/5
(786793)
Even in individuals who are unwilling to make prudent changes in their
diets and sedentary habits, the administration of certain nutrients and/or
drugs may help to prevent or postpone the onset of type 2 diabetes. The
evident ability of fiberrich cereal products to decrease diabetes risk,
as
documented in prospective epidemiological studies, may be mediated
primarily by the superior magnesium content of such foods. Highmagnesium
diets have preventive (though not curative) activity in certain rodent
models of diabetes; conversely, magnesium depletion provokes insulin
resistance. Epidemiology also strongly suggests that regular moderate
alcohol consumption has a major favorable impact on diabetes risk,
particularly in women; this may reflect a direct insulinsensitizing effect
on muscle and, in women, a reduced risk for obesity. Chromium picolinate
can also aid muscle insulin sensitivity. and initial reports suggest that
it is an effective therapy for type 2 diabetes. Highdose biotin has shown
therapeutic activity in diabetic rats and in limited clinical experience;
increased expression of glucokinase in hepatocytes may mediate this
benefit. Other nutrients that might prove to aid diabetic glycemic control,
and thus have potential for prevention, include coenzyme Q and conjugated
linoleic acids (CLA). Since the nutrients cited here including ethanol
in
moderation appear to be quite safe and (with the exception of CLA) quite
affordable, supplementation with these nutrients may prove to be a
practical strategy for diabetes prevention. Drugs such as metformin and
troglitazone, which are expensive and require regular physician monitoring
to avoid potentially dangerous sideeffects, would appear to be less
practical options from costeffectiveness, convenience and safety
standpoints, given the fact that the population atrisk for diabetes is
huge. (C) 2000 Harcourt Publishers Ltd.
13_ 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 148535601 United States
Nutrition Research ( NUTR. RES. ) (United States) 1992, 12/6 (787799)
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 biotindeficient 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.
14_ Biotinidase deficiency: presymptomatic treatment. Wallace SJ. Arch
Dis Child. 1985 Jun;60(6):5745.
Biotinidase deficiency presents with clinical signs of biotin deficiency
at the age of 3 months, or soon after. In an infant in whom the diagnosis
was made on cord blood, vision and hearing were normal before presymptomatic
treatment with biotin. Physical and mental development are good at 14
months.
15_ Longterm auditory and visual complications of biotinidase deficiency.
Taitz LS, Leonard JV, Bartlett K. Early Hum Dev 1985 Sep;11(34):32531
The biochemical, dermatological and neurological motor disorders of biotinidase
deficiency (multiple carboxylase deficiency) show a dramatic response
to pharmacological doses of biotin. This condition is characterised by
the accumulation of biocytin and depletion of biotin. Neuromuscular function
returns to normal with the reversal of the characteristic organic acidaemia.
It would appear that the optic and auditory nerves or their related neurological
structures may suffer damage from the excess biocytin and deficient biotin.
Despite reversal of the dermatological and psychomotor abnormalities children
are likely to be left with auditory and/or visual handicaps if diagnosis
and treatment is delayed beyond the first year of life. Treatment with
biotin was commenced 6, 18, and 13 months after onset of symptoms. Two
children subsequently were found to have visual impairment (acquired retinal
dysplasia) and two had sensorineural deafness. In one patient both defects
were present. Biotinidase deficiency: a survey of 10 cases.
16_ Wastell HJ, Bartlett K, Dale G, Shein A. Department of Clinical Biochemistry,
Newcastle General Hospital, Newcastle upon Tyne. Arch Dis Child 1988 Oct;63(10):12449
Ten patients with biotinidase deficiency were studied. Clinical findings
at presentation varied with dermatological signs (dermatitis and alopecia),
neurological abnormalities (fits, hypotonia, and ataxia), and recurrent
infections being the most common features, although none of these occurred
in every case. Biochemically the disease is characterised by metabolic
acidosis and organic aciduria. Treatment with biotin results in pronounced,
rapid, clinical and biochemical improvement, but some patients have residual
neurological damage comprising neurosensory hearing loss, visual pathway
defects, ataxia, and mental retardation. The cause of this permanent damage
remains obscure and it is not clear if the early introduction of treatment
will prevent it. Longterm auditory and visual complications of biotinidase
deficiency.
17_ Taitz LS, Leonard JV, Bartlett K. Early Hum Dev 1985 Sep;11(34):32531
The biochemical, dermatological and neurological motor disorders of biotinidase
deficiency (multiple carboxylase deficiency) show a dramatic response
to pharmacological doses of biotin. This condition is characterised by
the accumulation of biocytin and depletion of biotin. Neuromuscular function
returns to normal with the reversal of the characteristic organic acidaemia.
It would appear that the optic and auditory nerves or their related neurological
structures may suffer damage from the excess biocytin and deficient biotin.
Despite reversal of the dermatological and psychomotor abnormalities children
are likely to be left with auditory and/or visual handicaps if diagnosis
and treatment is delayed beyond the first year of life. Treatment with
biotin was commenced 6, 18, and 13 months after onset of symptoms. Two
children subsequently were found to have visual impairment (acquired retinal
dysplasia) and two had sensorineural deafness. In one patient both defects
were present.
18_ 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. (USA) , 1994, 132/2 (127132)
Rat liver phosphoenolpyruvate carboxykinase (PEPCK) activity was followed
over a time period of 5 h following administration of biotin to streptozotocininduced
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 runon 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. Therapeutic evaluation of the
effect of biotin on hyperglycemia in patients
19_ with noninsulin dependent diabetes mellitus. Maebashi Masaru; Makino
Yoshio; Furukawa Yuji(a); Ohinata Kosaku; Kimura Shuichi; Sato Takao Lab.
Nutr., Dep. Appl. Biol. Chem., Fac. Agric., Tohoku Univ., Aobaku, Sendai
981**Japan Journal of Clinical Biochemistry and Nutrition 1993 14 ( 3
): p 211218
The therapeutic efficacy of biotin was evaluated in 43 patients with
noninsulin dependent diabetes mellitus. The serum biotin concentration
in the patients was significantly lower than that in the 64 healthy control
subjects and inversely correlated with the fasting blood glucose level.
The oral administration of biotin, 9 mg daily, corrected the hyperglycemia
in the patients with no change in their serum insulin level. The serum
levels of pyruvate and lactate decreased to their normal ranges after
the administration. These observations suggest that the biotin administration
ameliorates abnormal glucose metabolism in diabetic patients, presumably
by enhancing the activity of the biotindependent enzyme, pyruvate carboxylase,
with a subsequent promotion of glucose utilization for the entry into
the tricarboxylic acid cycle. The administration also enhanced the response
to glibenclamide in patients who had been resistant to the agent, suggesting
a significant increase in the potency of the endogenous insulin action.
The result demonstrates that biotin administration is effective for the
treatment of the patients. Neither a relapse of clinical symptoms nor
an occurrence of undesirable side effects has been observed. Biotin for
diabetic peripheral neuropathy.
20_ Koutsikos D, Agroyannis B, TzanatosExarchou H. University of Athens,
Aretaieon University Hospital, Greece. Biomed Pharmacother 1990;44(10):5114
Biotin in high doses was given for 12 years to three diabetic patients
suffering from severe diabetic peripheral neuropathy. Within 48 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 biotindependent 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. Biotin supplementation improves glucose and insulin tolerances
in
21_ 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 JerseyNew Jersey Medical School, Newark,
NJ 071073006 USA LIFE SCI. (USA) , 1988, 42/13 (13231330)
Because biotin treatment may lower blood glucose in insulindependent
diabetes, we chose to study such an effect in noninsulin dependent diabetes.
Twentysix 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 postprandial glucose levels, and improved tolerance
to glucose and insulin resistance. Serum immunoreactive insulin levels
in biotintreated mice were like the controls. |