Regulation of beta cell function by Rev-erb alpha and the circadian clock

Abstract

Pancreatic islets are composed by different cell types, including insulin secreting ² cells, whose activity are modulated by circulating nutrients. Mechanisms of nutrient stimulated insulin secretion are still unknown. Recently, it was shown that the absence of clock genes Bmal1 and Clock in pancreatic islets reduces insulin secretion and causes hyperglycemia, indicating a participation of clock genes in ² cell function. Clock genes are auto-regulated and control the expression of other genes, known as clock controlled genes (ccg), like Dbp (D-box binding protein). Several peripheral tissues like liver, kidneys, heart and pancreatic islets have their functions regulated by clock genes, including glucose homeostasis.In this work we will evaluate clock genes involvement on glucose stimulated insulin secretion and reactive oxygen species production in pancreatic islets of Rev-erb± knockout mice and in a lineage of insulin secreting cells, INS 832/12, with low expression of Rev-erb± (shRNA - Rev-erb±). (AU)