Pancreatic α cells secrete glucagon, which controls blood glucose levels. In patients with type 1 or type 2 diabetes, hyperglycemia is often associated with hyperglucagonemia. High levels of glucagon have been shown to contribute to diabetic hyperglycemia. Thus, suppressing glucagon secretion could be a novel strategy for treating diabetes. However, the mechanism underlying excessive glucagon secretion is not fully understood. Glucose uptake into α cells was previously thought to be controlled solely by the passive glucose transporter GLUT1; however, a recent report described the expression of sodium glucose cotransporters 1 and 2 (SGLT1 and SGLT2) in α cells.
Suga et al. suggest that a novel mechanism regulates glucagon secretion through SGLT1 in α cells. Their findings may explain the distinct effects of selective SGLT2 inhibitors and mixed SGLT1/2 inhibitors on plasma glucagon levels in mice and might have implications for the classification and selection of SGLT2 inhibitors in the treatment of diabetes. Moreover, SGLT1 in α cells might contribute to the mechanism underlying hyperglucagonemia in diabetic patients.