title: Exenatide and biotin in conjunction with a protein-sparing fast for normalization of beta cell function in type 2 diabetics.
abstract: The dysdifferentiation of beta cells in type 2 diabetes appears to be caused and maintained by a vicious cycle of glucolipotoxicity: chronic elevations of glucose and free fatty acids induce beta cell dysdifferentiation as well as apoptosis; the resulting failure of glucose-stimulated insulin secretion tends to maintain the elevations of glucose and free fatty acids. Since extended fasts restore normoglycemia in diabetics, the resulting relief from glucotoxicity has been associated with a marked improvement in beta cell function that can be conserved after the fast if the factors precipitating diabetes--obesity, fatty and high-glycemic-index diets, sedentary lifestyle--have been adequately addressed. The new drug exenatide, an analog of the incretin hormone glucagon-like peptide-1, may be a worthwhile adjuvant to such fasting therapy, since it tends to counteract the glucolipotoxicity-induced down-regulation of the crucially important beta cell transcription factor IDX-1. Exenatide also exerts trophic effects on beta cell mass that in the longer term might help to restore diminished beta cell mass. Supraphysiological concentrations of biotin, possibly because they activate the soluble guanylate cyclase, also promote induction of IDX-1 and counteract the adverse impact of glucolipotoxicity in this regard; thus, high-dose biotin, which is well tolerated, may represent an additional adjuvant for therapeutic fasting intended to normalize beta cell function in type 2 diabetics.
authors.affiliation: Natural Alternatives International, 1185 Linda Vista Dr., San Marcos, CA 92078, USA. mccarty@pantox.com
authors.forename: Mark F
authors.initials: MF
authors.lastname: McCarty
mesh_terms: D001710:Biotin / Q000627:therapeutic use*; D002454:Cell Differentiation / Q000187:drug effects; D003131:Combined Modality Therapy; D003924:Diabetes Mellitus, Type 2 / Q000178:diet therapy / Q000188:drug therapy*; D018753:Diet, Protein-Restricted; D004359:Drug Therapy, Combination; D000077270:Exenatide; D005215:Fasting; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D010455:Peptides / Q000627:therapeutic use*; D014688:Venoms / Q000627:therapeutic use*
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D010455:Peptides; D014688:Venoms; D001710:Biotin; D000077270:Exenatide