グルカゴン分泌調節におけるSGLT2とAMPKの役割 – 糖尿病に対する薬物治療の観点から –

抄録

Recent studies have suggested the pathophysiological significance of glucagon in diabetes. SGLT2 inhibitors are clinically used to lower blood glucose levels independently of insulin, but a rise in blood glucagon level has got recognized as an adverse effect. The possible relevance of SGLT2 in pancreatic alpha cells was recently demonstrated, however, the roles of SGLT2, as well as its existence, in the alpha cells have been under intensive debate. Therefore, we conducted pharmacological analyses of SGLT2 in a typical model of the pancreatic alpha cell, α-TC cells to unveil roles of SGLT2 in the glucagon secretion, and happened to find involvement of AMPK in the off-target effects of one of the SGLT2 inhibitors on the regulation of glucagon secretion. In the current symposium, we would like to introduce our model of the possible molecular mechanisms regulating glucagon regulation in the α-TC cells, and the functional relevance of AMPK, ATP, and SGLT2 in the pancreatic alpha cells will be discussed.