Dapagliflozin stimulates glucagon secretion at high glucose: experiments and mathematical simulations of human A-cells.

ABSTRACT: Glucagon is one of the main regulators of blood glucose levels and dysfunctional stimulus secretion coupling in pancreatic A-cells is believed to be an important factor during development of diabetes. However, regulation of glucagon secretion is poorly understood. Recently it has been shown that Na(+)/glucose co-transporter (SGLT) inhibitors used for the treatment of diabetes increase glucagon levels in man. Here, we show experimentally that the SGLT2 inhibitor dapagliflozin increases glucagon secretion at high glucose levels both in human and mouse islets, but has little effect at low glucose concentrations. Because glucagon secretion is regulated by electrical activity we developed a mathematical model of A-cell electrical activity based on published data from human A-cells. With operati

SUBMITTER: Pedersen MG 

PROVIDER: S-EPMC4989223 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature