Role of crosstalk between peripheral circadian clock and NO-cGMP system of pancreatic beta-cells in the pathogenesis of diabetes

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This study was aimed to investigate the relation between the regulation of NO-cGMP system by the endogenous NO synthase inhibitor ADMA and peripheral circadian clock in pancreatic beta-cells and the involvement of these systems in the pathogenesis of diabetes. We found that the expression of the ADMA metabolic enzyme DDAH2 in beta-cells is suppressed by high glucose, suggesting that the NO-cGMP system is down-regulated by the accumulation of ADMA in diabetes. Unfortunately, we could not obtain any evidence for a relation between the NO-cGMP system and peripheral circadian clock in beta-cells. On the other hand, melatonin, a circadian synchronizer, was suggested to inhibit insulin secretion from beta-cells in the presence of GLP-1 secreted from the gastrointestinal mucosa in response to a meal. Thus, the possibility is raised that some relation between food intake and circadian rhythm exists in the regulation of beta-cell functions.