Prolonged high glucose exposure alters beta cell function

Diabetes mellitus affects nearly 600,000,000 people globally and is the eighth leading cause of death in the United States. Symptoms of diabetes include decreased insulin secretion and impaired glucose tolerance, both of which lead to weight gain and many other health challenges. Both type 1 and 2 diabetes result in decreased functional pancreatic beta cell mass. ProlongedJT1 elevated glucose levels are characteristic of a diabetic disease state. Physiological glucose levels usually rest at the baseline fasting state (5 mM Glucose) and spikes high in the fed state (11 mM Glucose), after which it returns to the baseline level. Glucose starts signaling cascades in various cell types, including beta cells. Here we demonstrate the effect of 24-hour 5 mM vs 11 mM glucose treatment on INS-1 beta cell gene expression. In GO analyses of 5 mM vs 11 mM INS-1 RNA sequencing data, eight of the fifteen top upregulated terms were associated with proliferation, including chromosome segregation and chromosome organization. Additionally, twelve of the fifteen most downregulated GO terms were associated with insulin secretion, including insulin metabolic process and peptide hormone secretion. These analyses are supported by KEGG analysis, which shows upregulation of cell cycle and TCA cycle, as well as downregulation of insulin secretion. We see that Ins1 and Ins2 mRNA levels are decreased in 11 mM glucose-treated cells. The 11 mM-treated cells also demonstrate altered glucose stimulated insulin secretion. We confirmed that 11 mM glucose-treated cells have greater proliferation as demonstrated via thymidine incorporation, as well as higher mitochondrial respiration. From this data, we see that prolonged high glucose treatment causes significant physiological changes in the beta cell. Understanding these changes is essential for understanding beta cell health during T1D and T2D, and studies are ongoing. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.