SGLT2-i improves markers of islet endothelial cell function in db/db diabetic mice

Area of Science:

• Endocrinology
• Vascular Biology
• Pharmacology

Background:

• Islet endothelial cells are crucial for beta-cell function and survival.
• Type 2 diabetes is associated with dysfunctional islet endothelial cells, characterized by increased inflammation and cellular adhesion.
• Hyperglycemia exacerbates endothelial dysfunction in pancreatic islets.

Purpose of the Study:

• To investigate the effects of empagliflozin and metformin on islet endothelial cell function in a mouse model of type 2 diabetes.
• To assess if improvements in endothelial function correlate with enhanced insulin secretion and glycemic control.
• To compare the efficacy of empagliflozin and metformin, alone and in combination.

Main Methods:

• db/db diabetic mice and non-diabetic controls were treated with empagliflozin, metformin, or combination therapy for 6 weeks.
• Gene expression of islet endothelial dysfunction markers was quantified.
• Islet morphometry, plasma glucose, and insulin secretion during intravenous glucose tolerance tests were assessed.

Main Results:

• Diabetic mice exhibited increased expression of endothelial dysfunction marker genes.
• Empagliflozin and metformin treatment reduced the expression of these markers, correlating with improved glycemic control and insulin release.
• Empagliflozin was more effective than metformin alone; the combination therapy showed the most significant improvements.

Conclusions:

• Empagliflozin and metformin treatment can ameliorate islet endothelial cell dysfunction in type 2 diabetes.
• Improving islet endothelial function is a potential therapeutic strategy for enhancing insulin release in type 2 diabetes.
• Combination therapy with empagliflozin and metformin offers a promising approach for managing type 2 diabetes.