Dysregulation of Glucagon Secretion by Hyperglycemia-Induced Sodium-Dependent Reduction of ATP Production (Cell Metabolism)

In diabetes, glucagon secretion is dysregulated but the underlying mechanisms are not fully understood. Knudsen et al. report that hyperglycemia impairs glucagon secretion by SGLT-dependent elevation of intracellular Na+, leading to acidification, reduced ATP production, and dysregulated KATP channel activity in ? cells. The SGLT mechanism may also impair heart and kidney cell ATP production.