Dapagliflozin improves pancreatic islet function by attenuating microvascular endothelial dysfunction in type 2...

Area of Science:

• Endocrinology
• Diabetology
• Vascular Biology

Background:

• Sodium-glucose co-transporter 2 inhibitors (SGLT2i) like dapagliflozin benefit type 2 diabetes by improving beta cell function.
• The protective effects of dapagliflozin on islet microvascular endothelial cells (IMECs) and their contribution to beta cell function remain unclear.

Purpose of the Study:

• To investigate whether dapagliflozin protects IMECs and if this mechanism contributes to improved beta cell function in type 2 diabetes.

Main Methods:

• Treatment of db/db mice with dapagliflozin to assess beta cell function, islet vascularization, and IMEC inflammation.
• In vitro studies using MS-1 cells (IMEC cell line) and MIN6 cells (beta cell line) to evaluate angiogenesis, chemokine levels, and beta cell function under dapagliflozin treatment.
• Analysis of PI3K/Akt-mTOR signaling pathways involved in dapagliflozin's effects.

Main Results:

• Dapagliflozin treatment in db/db mice enhanced islet capillaries, reduced IMEC inflammation, and improved beta cell function.
• In vitro, dapagliflozin promoted angiogenesis and reduced inflammation in MS-1 cells, effects mediated by the PI3K/Akt-mTOR pathway.
• Dapagliflozin protected beta cell function and insulin secretion in MIN6 cells co-cultured with MS-1 cells, but not in monoculture.

Conclusions:

• Dapagliflozin restores islet vascularization and reduces IMEC inflammation in type 2 diabetic models.
• The beneficial effects of dapagliflozin on beta cell function are partly attributed to its protective actions on IMECs via the PI3K/Akt-mTOR pathway.