Protein Kinase C (Pkc)-delta Mediates Arginine-Induced Glucagon Secretion in Pancreatic alpha-Cells

The pathophysiology of type 2 diabetes involves insulin and glucagon. Protein kinase C (Pkc)-delta, a serine-threonine kinase, is ubiquitously expressed and involved in regulating cell death and proliferation. However, the role of Pkc delta in regulating glucagon secretion in pancreatic alpha-cells remains unclear. Therefore, this study aimed to elucidate the physiological role of Pkc delta in glucagon secretion from pancreatic alpha-cells. Glucagon secretions were investigated in Pkc delta-knockdown InR1G9 cells and pancreatic alpha-cell-specific Pkc delta-knockout (alpha Pkc delta KO) mice. Knockdown of Pkc delta in the glucagon-secreting cell line InR1G9 cells reduced glucagon secretion. The basic amino acid arginine enhances glucagon secretion via voltage-dependent calcium channels (VDCC). Furthermore, we showed that arginine increased Pkc delta phosphorylation at Thr(505), which is critical for Pkc delta activation. Interestingly, the knockdown of Pkc delta in InR1G9 cells reduced arginine-induced glucagon secretion. Moreover, arginine-induced glucagon secretions were decreased in alpha Pkc delta KO mice and islets from alpha Pkc delta KO mice. Pkc delta is essential for arginine-induced glucagon secretion in pancreatic alpha-cells. Therefore, this study may contribute to the elucidation of the molecular mechanism of amino acid-induced glucagon secretion and the development of novel antidiabetic drugs targeting Pkc delta and glucagon.