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.