Visfatin inhibits insulin biosynthesis and secretion in pancreatic β-cells

The recently identified adipocytokine visfatin has insulin-mimetic properties and a role of visfatin in the regulation of glucose metabolism has been suggested. In human obesity and in animal models of obesity, the pancreas is embedded in adipose tissue and we could frequently observe adipocytes located within the pancreas in close proximity to the insulin producing islets. We therefore investigated the direct effect of visfatin on pancreatic β-cell insulin production and secretion in vitro in primary isolated rat pancreatic islets and in the rat Ins-1 insulinoma cell line. Incubation of primary isolated rat islets as well as Ins-1 cells with visfatin for 24 hours significantly reduced intracellular insulin stores in a dose dependent manner. The reduction of intracellular insulin levels was also reflected on the ultrastructural level, where a reduction of β-cell granules was observed in visfatin-treated Ins-1 cells. The inhibition of insulin production by visfatin was the result of a decreased transcription of the preproinsulin-1 gene in primary cells and Ins-1 cells and of the preproinsulin-2 gene in Ins-1 cells. In addition, low glucose as well as sustained glucose-stimulated insulin secretion was inhibited by visfatin. In conclusion, these findings demonstrate direct suppressive effects of visfatin on insulin gene expression and consequently insulin secretion. We suggest that in obese individuals the increased expression and release of visfatin from visceral adipose tissue could contribute to the pathogenesis of β-cell dysfunction, and consequently contribute to the development of type 2 diabetes mellitus.