Work

Dapagliflozin suppresses glucagon signaling in rodent models of diabetes

Year: 2017

Type: article

Abstract: Significance Sodium-glucose cotransporter 2 (SGLT2) inhibitors lower blood glucose in humans with diabetes. These drugs inhibit the reabsorption of glucose in the kidney, resulting in its urine excretion. It was reported that SGLT2 inhibitors increase the secretion of glucagon and increase endogenous glucose production by the liver. These effects would elevate blood glucose, counteracting the effect of urinary glucose loss. Here we show in a rodent model of type 1 diabetes that the SGLT2 inhibitor dapagliflozin inhibited the secretion of glucagon from the pancreas. In two rodent models of severe type 2 diabetes, livers from animals treated with dapagliflozin showed decreased glucagon signaling and had reduced expression of the glucagon receptor. Our results suggest dapagliflozin lowers blood glucose concentrations in diabetic animals in part through inhibiting hepatic glucagon signaling.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.1705845114