Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Incretin hormones have trophic effects on beta cell function that can aid prevention and treatment of diabetes. cAMP is the primary mediator of these effects, and has been shown to potentiate glucose-stimulated insulin secretion, promote proper beta cells differentiation by increasing expression of the crucial transcription factor PDX-1, and prevent beta cell apoptosis. cGMP's role in beta cell function has received far less scrutiny, but there is emerging evidence that it may have a trophic impact on beta cell function analogous to that of cAMP. An increase in plasma glucose boosts beta cell production of cGMP, which acts as a feed-forward mediator to enhance glucose-stimulated insulin secretion. cGMP also has an anti-apoptotic effect in beta cells, and there is now indirect evidence that it promotes expression of PDX-1. Supraphysiological concentrations of biotin can directly activate guanylate cyclase, and there is limited evidence that high intakes of this vitamin can be therapeutically beneficial in diabetics and in rodent models of diabetes. Beneficial effects of cGMP on muscle insulin sensitivity and on control of hepatic glucose output may contribute to biotin's utility in diabetes. The fact that nitric oxide/cGMP exert a range of favorable effects on vascular health should further encourage exploration of biotin's preventive and therapeutic potential. If an appropriate high-dose biotin regimen could achieve a modest systemic increase in guanylate cyclase activity, without entailing unacceptable side effects or risks, such a regimen might have considerable potential for promoting vascular health and preventing or managing diabetes.
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PMID:cGMP may have trophic effects on beta cell function comparable to those of cAMP, implying a role for high-dose biotin in prevention/treatment of diabetes. 1630 50

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.
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PMID:Exenatide and biotin in conjunction with a protein-sparing fast for normalization of beta cell function in type 2 diabetics. 1729 59