SGLT1 in pancreatic α cells regulates glucagon secretion in mice, possibly explaining the distinct effects of SGLT2 inhibitors on plasma glucagon levels.

ABSTRACT:

Objectives

It is controversial whether sodium glucose transporter (SGLT) 2 inhibitors increase glucagon secretion via direct inhibition of SGLT2 in pancreatic α cells. The role of SGLT1 in α cells is also unclear. We aimed to elucidate these points that are important not only for basic research but also for clinical insight.

Methods

Plasma glucagon levels were assessed in the high-fat, high-sucrose diet (HFHSD) fed C57BL/6J mice treated with dapagliflozin or canagliflozin. RT-PCR, RNA sequence, and immunohistochemistry were conducted to test the expression of SGLT1 and SGLT2 in α cells. We also used αTC1 cells and mouse islets to investigate the molecular mechanism by which SGLT1 modulates glucagon secretion.

Results

Dapagliflozin, but not canagliflozin, increased pla

SUBMITTER: Suga T 

PROVIDER: S-EPMC6323192 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature