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Dapagliflozin improves pancreatic islet function by attenuating microvascular endothelial dysfunction in type 2 diabetes.
- Source :
- Diabetes/Metabolism Research & Reviews; Mar2023, Vol. 39 Issue 3, p1-13, 13p
- Publication Year :
- 2023
-
Abstract
- Aims: Sodium‐glucose co‐transporter 2 inhibitors, including dapagliflozin, improve ß cell function in type 2 diabetic individuals. Whether dapagliflozin can protect islet microvascular endothelial cells (IMECs) and thus contribute to the improvement of ß cell function remains unknown. Materials and Methods: The db/db mice were treated with dapagliflozin or vehicle for 6 weeks. ß cell function, islet capillaries and the levels of inflammatory chemokines in IMECs were detected. The mouse IMEC cell line MS‐1 cells were incubated with palmitate and/or dapagliflozin for 24 h. Angiogenesis and inflammatory chemokine levels were evaluated, and the involved signalling pathways were analysed. The mouse ß cell line MIN6 cells, in the presence or absence of co‐culture with MS‐1 cells, were treated with palmitate and/or dapagliflozin for 24 h. The expression of ß cell specific markers and insulin secretion in MIN6 cells were determined. Results: Dapagliflozin significantly improved ß cell function, increased islet capillaries and decreased the levels of inflammatory chemokines of IMECs in db/db mice. In the palmitate‐treated MS‐1 cells, angiogenesis was enhanced and the levels of inflammatory chemokines were downregulated by dapagliflozin. Either a PI3K inhibitor or mTOR inhibitor eliminated the dapagliflozin‐mediated effects. Importantly, dapagliflozin attenuated the palmitate‐induced downregulation of ß cell function‐related gene expression and insulin secretion in MIN6 cells co‐cultured with MS‐1 cells but not in those on mono‐culture. Conclusions: Dapagliflozin restores islet vascularisation and attenuates the inflammation of IMECs in type 2 diabetic mice. The dapagliflozin‐induced improvement of ß cell function is at least partially accounted for by its beneficial effects on IMECs in a PI3K/Akt‐mTOR‐dependent manner. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15207552
- Volume :
- 39
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- Diabetes/Metabolism Research & Reviews
- Publication Type :
- Academic Journal
- Accession number :
- 162242686
- Full Text :
- https://doi.org/10.1002/dmrr.3607