MAP kinases and their roles in pancreatic beta-cells.

We discuss our work examining regulation and functions of mitogen-activated protein kinases, particularly ERK1 and ERK2, in pancreatic beta-cells. These enzymes are activated by glucose, other nutrients, and insulinogenic hormones. Their activation by these agents is calcium-dependent. A number of other stimuli also activate ERK1/2, but by mechanisms distinct from those involved in nutrient sensing. Inhibition of ERK1/2 has no apparent effect on insulin secretion measured after 2 h. On the other hand, ERK1/2 activity is required for maximal glucose-dependent activation of the insulin gene promoter. The primary effort has focused on INS-1 cell lines, with supporting and confirmatory studies in intact islets and other beta-cell lines, indicating the generality of our findings in beta-cell function. Thus ERK1/2 participate in transmitting glucose-sensing information to beta-cell functions. These kinases most likely act directly and indirectly on multiple pathways that regulate beta-cell function and, in particular, to transduce an elevated glucose signal into insulin gene transcription.