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Diabetes and Vascular Disease

MON-541 - Β-Cell Gαz Loss Is Not Sufficient to Protect Against Disease in A Nonobese Diabetic Mouse Model of Type 1 Diabetes

Monday, June 15, 2026
9:00 AM - 2:00 PM CT
Location: ENDOExpo; Poster Floor
Disclosure(s):
Amanda Allender, MS, BS: No financial relationships to disclose
Type 1 diabetes is characterized by immune-cell destruction of insulin-producing β-cells, resulting in decreased functional β-cell mass and impaired insulin secretion. G proteins in the β-cell can regulate insulin secretion to maintain blood glucose levels. Prior work in our lab has shown that a full body knockout of the G protein Gαz, which has limited tissue expression throughout the body, is protective against diabetes development in the nonobese diabetic (NOD) mouse model of type 1 diabetes. We hypothesized that this protection is β-cell autonomous, and that a β-cell specific knockout (βKO) of Gαz would be sufficient to protect NOD mice from diabetes development. This longitudinal study shows that female Gαz βKO mice are not protected against diabetes development despite improved glucose tolerance during acute oral glucose challenge. We used histological approaches such as immunofluorescence, immunohistochemistry, and islet immune-cell infiltration to assess β-cell health in dissected mouse pancreata. When possible, histological analysis was blinded to genotype and carried out by two individuals. Critically, this lack of protection against diabetes development is accompanied by no significant changes in β-cell replication, apoptosis, mass, or immune-cell infiltration severity. Thus, the improved glucose tolerance following acute oral glucose challenge is not due to improved β-cell health and is due to some other mechanism. Current work is underway to 1) determine the mechanism of the improved glucose tolerance and to 2) determine why the β-cell knock out model was not protected against diabetes development. Preliminary protein expression data indicates novel tissue expression of Gαz that may contribute to the lack of protection observed in the βKO model, an explanation we are currently exploring.

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