Dapagliflozin does not directly affect human α or β cells.

Dapagliflozin does not directly affect human α or β cells. Endocrinology. 2020 May 19;: Authors: Dai C, Walker JT, Shostak A, Bouchi Y, Poffenberger G, Hart NJ, Jacobson DA, Calcutt MW, Bottino R, Greiner DL, Shultz LD, McGuinness OP, Dean ED, Powers AC Abstract Selective inhibitors of sodium glucose cotransporter-2 (SGLT2) are widely used for the treatment of type 2 diabetes (T2D) and act primarily to lower blood glucose by preventing glucose reabsorption in the kidney. However, it is controversial whether these agents also act on the pancreatic islet, specifically the α cell, to increase glucagon secretion. To determine the effects of SGLT2 on human islets, we analyzed SGLT2 expression and hormone secretion by human islets treated with the SGLT2 inhibitor dapaglifozin (DAPA) in vitro and in vivo. Compared to the human kidney, SLC5A2 transcript expression was 1600-fold lower in human islets and SGLT2 protein was not detected. In vitro, DAPA treatment had no effect on glucagon or insulin secretion by human islets at either high or low glucose concentrations In mice bearing transplanted human islets, 1 and 4 weeks of DAPA treatment did not alter fasting blood glucose, human insulin, and total glucagon levels. Upon glucose stimulation, DAPA treatment led to lower blood glucose and proportionally lower human insulin, irrespective of treatment duration. In contrast, after glucose stimulation total glucagon was increased after 1 week o...
Source: Endocrinology - Category: Endocrinology Authors: Tags: Endocrinology Source Type: research