Conclusion
In male ZDF rats, chronic imeglimin treatment corrects a paramount component of type 2 diabetes progression: progressive loss of functional β-cell mass. In addition, imeglimin may also moderate a-cell turnover to further ameliorate hyperglycaemia. Cumulatively, these cellular effects suggest that imeglimin may provide for disease modifying effects to preserve functional β-cell mass.
Methods
Zucker diabetic fatty (ZDF) male rats were treated by oral gavage with imeglimin at a standard dose of 150 mg/kg or vehicle, twice daily for five weeks. At treatment completion, oral glucose tolerance tests were performed in fasted animals before a thorough histomorphometry and immunohistochemical analysis was conducted on pancreas tissue slices to assess cellular composition and disease status.
Results
Imeglimin treatment significantly improved glucose-stimulated insulin secretion (augmentation of the insulinogenic index) and improved glycaemia. Both basal insulinaemia and pancreatic insulin content were also increased by imeglimin. In ZDF control rats, islet structure was disordered with few β-cells; after imeglimin treatment, islets appeared healthier with more normal morphology in association with a significant increase in insulin-positive β-cells. The increase in β-cell mass was associated with a greater degree of β-cell proliferation in the presence of reduced apoptosis. Unexpectedly, a decrease in as a α-cell mass was also documented due to an apparent antiproliferative effect of imeglimin on this cell type.