In type 1 diabetics, high-dose biotin may compensate for low hepatic insulin exposure, promoting a more normal expression of glycolytic and gluconeogenic enyzymes and thereby aiding glycemic control.
In type 1 diabetics, hepatic exposure to insulin is chronically subnormal even in the context of insulin therapy; as a result, expression of glycolytic enzymes is decreased, and that of gluconeogenic enzymes is enhanced, resulting in a physiologically inappropriate elevation of hepatic glucose output. Subnormal expression of glucokinase (GK) is of particular importance in this regard. Possible strategies for correcting this perturbation of hepatic enzyme expression include administration of small molecule allosteric activators of GK, as well as a procedure known as chronic intermittent intravenous insulin therapy (CIIIT); however, side effects accompany the use of GK activators, and CIIIT is time and labor intensive. Alternatively, administration of high-dose biotin has potential for modulating hepatic enzyme expression in a favorable way. Studies in rodents and in cultured hepatocytes demonstrate that, in the context of low insulin exposure, supra-physiological levels of biotin induce increased expression of GK while suppressing that of the key gluconeogenic enzyme phosphoenolpyruvate carboxykinase. These effects may be a downstream consequence of the fact that biotin down-regulates mRNA expression of FOXO1; insulin's antagonism of the activity of this transcription factor is largely responsible for its modulatory impact on hepatic glycolysis and gluconeogenesis. Hence, high-dose biotin may compensate for subnormal insulin exposure by suppressing FOXO1 levels. High-dose biotin also has the potential to oppose hepatic steatosis by down-regulating SREBP-1 expression. Two pilot trials of high-dose biotin (16 or 2mg per day) in type 1 diabetics have yielded promising results. There is also some reason to suspect that high-dose biotin could aid control of diabetic neuropathy and nephropathy via its stimulatory effect on cGMP production. Owing to the safety, good tolerance, moderate expense, and current availability of high-dose biotin, this strategy merits more extensive evaluation in type 1 diabetes.
Catalytic Longevity, 7831 Rush Rose Drive, Apt. 316, Carlsbad, CA 92009, United States. Electronic address: markfmccarty@gmail.com.
Mark F
MF
McCarty
D000495:Allosteric Site; D000818:Animals; D001710:Biotin / Q000737:chemistry* / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism; D002986:Clinical Trials as Topic; D003921:Diabetes Mellitus, Experimental; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D000071161:Forkhead Box Protein O1 / Q000378:metabolism; D005786:Gene Expression Regulation; D005941:Glucokinase / Q000378:metabolism; D005943:Gluconeogenesis; D006019:Glycolysis; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism / Q000627:therapeutic use*; D008099:Liver / Q000378:metabolism; D018384:Oxidative Stress; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism
D001786:Blood Glucose; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D007328:Insulin; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D001710:Biotin; D005941:Glucokinase
Biotin; FOXO1; Glucokinase; Gluconeogenesis; SREBP-1; Type 1 diabetes