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Updated: Jun 26, 2026
05:18
A Protocol for Constructing a Rat Wound Model of Type 1 Diabetes
Published on: February 17, 2023
SGLT2 Inhibitors Promote Diabetic Wound Healing Via AMPK/AKT/mTORC1-Regulated Endothelial Angiogenesis
Furkan Bestepe1, George F Ghanem1, Caroline Kelly1
1Department of Medicine, Molecular Cardiology Research Institute (F.B., G.F.G., C.K., K.H., D.V.R., R.B., A.Z., P. Sahu, G.S.H., B.I.), Tufts Medical Center, Boston, MA.
Arteriosclerosis, Thrombosis, and Vascular Biology
|June 25, 2026
Summary
Empagliflozin and dapagliflozin significantly improve diabetic wound healing by promoting angiogenesis, unlike canagliflozin. These SGLT2 inhibitors balance AMPK/AKT/mTORC1 signaling for better endothelial cell function and wound repair.
Area of Science:
- Endocrinology and Metabolism
- Vascular Biology
- Wound Healing Research
Background:
- Diabetic ulcers affect 25% of type 2 diabetes patients, with impaired angiogenesis being a key challenge.
- Sodium-glucose transporter 2 (SGLT2) inhibitors are known for cardiovascular and renal benefits, but their role in wound healing and angiogenesis is unclear.
Purpose of the Study:
- To investigate the distinct effects of SGLT2 inhibitors (empagliflozin, dapagliflozin, canagliflozin) on diabetic wound healing and angiogenesis.
- To elucidate the underlying molecular mechanisms involving AMPK/AKT/mTORC1 signaling pathways.
Main Methods:
- Evaluated wound healing in db/db mice, assessing closure, granulation tissue, and perfusion.
- Utilized CD31 and Ki67 immunostaining for angiogenesis and proliferation.
- Conducted ex vivo (human skin organoids, microvessels, aortic explants) and in vitro (endothelial cells) studies.
Main Results:
- Empagliflozin and dapagliflozin significantly enhanced wound healing, angiogenesis, and proliferation; canagliflozin showed limited benefit.
- Empagliflozin and dapagliflozin promoted sprouting angiogenesis and increased tissue remodeling gene expression.
- Distinct effects on AMPK/AKT/mTORC1 signaling were observed: canagliflozin excessively activated AMPK and suppressed AKT/mTORC1.
Conclusions:
- Empagliflozin and dapagliflozin promote endothelial cell-angiogenic functions via balanced AMPK/AKT/mTORC1 signaling.
- Canagliflozin impaired these processes through excessive AMPK activation, hindering wound healing.
- Restoring balanced signaling pathways is crucial for effective diabetic wound healing.
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