SGLT2 is not expressed in pancreatic alpha and beta cells and its inhibition does not directly affect glucagon and insulin secretion in rodents and humans

BACKGROUND AND AIMS: SGLT2 inhibitors (SGLT2i), such as dapagliflozin and empagliflozin, are effective glucose-lowering medications with a unique, insulin-independent mechanism that is to promote glycosuria. SGTL2i-induced glycosuria is associated with metabolic responses including increases in fatty acid mobilization, hepatic glucose and ketone body production, and circulating glucagon levels. These metabolic adaptations are considered causative for rare cases of euglycemic ketoacidosis reported for SGLT2i. One potential cause of euglycemic ketoacidosis is the SGLT2i-mediated increase in glucagonemia and drop in insulinemia. It has been suggested that direct inhibition of α-cell SGLT2 stimulates glucagon release. Here, we investigated the potential role of SGLT1 and SGLT2 in the control of glucagon and insulin secretion from rat, mouse and human islets [...