Exenatide and biotin in conjunction with a protein-sparing fast for normalization of beta cell function in type 2 diabetics
Section snippets
Fasting as a strategy for normalizing diabetic beta cell function
The relative failure of glucose-stimulated insulin secretion in type 2 diabetics – especially the loss of the first-phase response – appears to reflect a dysdifferentiation of beta cells that is induced and maintained by chronic glucolipotoxicity [1], [2], [3], [4]. The resulting failure of beta cells to respond properly to elevations in serum glucose tends to perpetuate the chronic elevation of glucose and free fatty acids, thus leading to a vicious cycle that maintains beta cell failure.
A role for exenatide in beta cell redifferentiation therapy
The novel drug exenatide, an analog of glucagon-like peptide-1 (GLP-1) found in the saliva of gila monsters, is now approved as an insulinotropic therapy for type 2 diabetics [23], [24]. By acting as an agonist for GLP-1 receptors on beta cells – which increase cAMP production in these cells – exenatide acts to potentiate insulin secretion in response to a rise in plasma glucose, just like natural incretin hormones do [25]. However, unlike sulphonylureas, GLP-1 and exenatide cannot promote beta
High-dose biotin may complement these benefits
The vitamin biotin, which in modestly supraphysiological concentrations (0.1–1 μM) can directly activate soluble guanylate cyclase [42], [43], [44] – albeit less dramatically than nitric oxide can – has replicated many of the favorable effects of GLP-1 on beta cell function and differentiation in cell culture and rodent studies. Thus, biotin potentiates the insulin secretory response to elevated glucose (without directly provoking insulin secretion), and also boosts expression of IDX-1 and of
A prudent lifestyle required to preserve normalized beta cell function
In diabetic patients who manage to achieve substantial weight loss, and who become dedicated to regular exercise and prudent eating, diabetes is sometimes reversible without ancillary measures [64]. However, in selected patients in whom such efforts nonetheless fail to normalize beta cell function, a protein-sparing fast of moderate duration (for example, a week to 10 days), coupled with concurrent exenatide and biotin therapy, may have the potential to restore normal beta cell differentiation
References (64)
- et al.
Glucose down-regulates the expression of the peroxisome proliferator-activated receptor-alpha gene in the pancreatic beta-cell
J Biol Chem
(2000) Incorporation of beta cell redifferentiation therapy into a lipoprivic strategy for reversing type 2 diabetes
Med Hypotheses
(2002)- et al.
Fatty acids decrease IDX-1 expression in rat pancreatic islets and reduce GLUT2, glucokinase, insulin, and somatostatin levels
J Biol Chem
(1997) - et al.
Effects of very-low-calorie diet weight reduction on glucose tolerance, insulin secretion, and insulin resistance in obese non-insulin-dependent diabetics
Diabetes Res Clin Pract
(1989) - et al.
Very low calorie diet (VLCD): a useful alternative in the treatment of the obese NIDDM patient
Diabetes Res Clin Pract
(1997) - et al.
Pharmacology of exenatide (synthetic exendin-4): a potential therapeutic for improved glycemic control of type 2 diabetes
Regul Pept
(2004) - et al.
Enhanced expression of PDX-1 and Ngn3 by exendin-4 during beta cell regeneration in STZ-treated mice
Biochem Biophys Res Commun
(2005) - et al.
Effects of biotin upon the intracellular level of cGMP and the activity of glucokinase in cultured rat hepatocytes
J Biol Chem
(1984) - et al.
Effects of biotin on glucotoxicity or lipotoxicity in rat pancreatic islets
Metabolism
(2002) - et al.
Nitric oxide-cyclic GMP system potentiates glucose-induced rise in cytosolic Ca2+ concentration in rat pancreatic beta-cells
Life Sci
(1999)
Two distinct effects of cGMP on cytosolic Ca2+ concentration of rat pancreatic beta-cells
J Pharmacol Sci
Effects of biotin on pyruvate carboxylase, acetyl-CoA carboxylase, propionyl-CoA carboxylase, and markers for glucose and lipid homeostasis in type 2 diabetic patients and nondiabetic subjects
Am J Clin Nutr
Biotin supplementation improves glucose and insulin tolerances in genetically diabetic KK mice
Life Sci
High-dose biotin, an inducer of glucokinase expression, may synergize with chromium picolinate to enable a definitive nutritional therapy for type II diabetes
Med Hypotheses
Beta-cell dysfunction induced by chronic hyperglycemia. Current ideas on mechanism of impaired glucose-induced insulin secretion
Diabetes Care
Lipotoxicity in the pathogenesis of obesity-dependent NIDDM. Genetic and clinical implications
Diabetes
Reduced insulin, GLUT2, and IDX-1 in beta-cells after partial pancreatectomy
Diabetes
Transcription factor abnormalities as a cause of beta cell dysfunction in diabetes: a hypothesis
Acta Diabetol
PDX-1 induces insulin and glucokinase gene expressions in alpha TC1 clone 6 cells in the presence of betacellulin
Diabetes
A newly discovered role of transcription factors involved in pancreas development and the pathogenesis of diabetes mellitus
Proc Assoc Am Physicians
PDX-1 induces differentiation of intestinal epithelioid IEC-6 into insulin-producing cells
Diabetes
PDX-1 and the pancreas
Pancreas
Prolonged fasting in diabetes
Am J Med Sci
Fasting and eating for health
Malonyl-CoA signaling, lipid partitioning, and glucolipotoxicity: role in beta-cell adaptation and failure in the etiology of diabetes
Diabetes
Beta-cell glucose toxicity, lipotoxicity, and chronic oxidative stress in type 2 diabetes
Diabetes
Very low calorie diet therapy in obese non-insulin dependent diabetes patients
Int J Obes
Effects of VLCD in obese NIDDM (non-insulin dependent diabetes) on glucose, insulin and C-peptide dynamics
Int J Obes
Effects of a very-low-calorie diet on long-term glycemic control in obese type 2 diabetic subjects
Arch Int Med
Benefits and limitations of very-low-calorie diet therapy in obese NIDDM
Diabetes Care
Caloric restriction per se is a significant factor in improvements in glycemic control and insulin sensitivity during weight loss in obese NIDDM patients
Diabetes Care
Incretin mimetics as emerging treatments for type 2 diabetes
Ann Pharmacother
Cited by (4)
NAPDH oxidase mediates glucolipotoxicity-induced beta cell dysfunction - Clinical implications
2010, Medical HypothesesMicroarray analysis of pancreatic gene expression during biotin repletion in biotin-deficient rats
2015, Canadian Journal of Physiology and PharmacologyMechanism of the beneficial and protective effects of exenatide in diabetic rats
2014, Journal of Endocrinology