1766-P: Pick1 Regulates Glucose Homeostasis and Insulin Secretion through the MAPK Pathway

Adult patients with a dysfunctional Protein interacting with C-kinase 1 (PICK1) present with hyperinsulinemia and hyperglycemia. PICK1 was reported to be a peripheral membrane protein that controled insulin granule formation, trafficking, and maturation in INS-1E cells. However, the mechanism of Pick1 in glucose metabolism disorders has not been clearly defined. Here, we demonstrate that Pick1 β-cell-specific knockout (βKO) had impaired glucose tolerance and decreased insulin serection. By contrast, overexpression of Pick1 in primary pancreatic β-cells led to apoptosis. Similarly, induction of Pick1 by tail vein injection into βKO mice improved glucose tolerance by reducing apoptosis. Furthermore, we show that Pick1 alleviated apoptosis and inflammation via the mitogen activated protein kinase (MAPK) pathway both in vitro and in vivo. In summary, our study provides new insights into the causes of primary pancreatic β-cells apoptosis.