Effects of palmitate and oleate on pancreatic beta cell function

Type 2 diabetes mellitus (T2D) is a chronic metabolic disorder affecting an estimated 35 million Americans. Diabetes is characterized by persistent serum hyperglycemia and hyperlipidemia, which collectively cause glucolipotoxicity in pancreatic beta cells. Glucolipotoxicity reduces beta cell survival, proliferation, and functionality. Oleate and palmitate are two of the most prevalent fatty acids in circulation in T2D. Palmitate has negative effects on beta cells, while oleate may have positive effects. Here we demonstrate the effects of 2mM oleate or 2mM palmitate treatment on INS-1 beta cells. We performed RNA sequencing, and our data shows that proliferation related pathways (chromosome segregation, nuclear division, etc.) are downregulated by both palmitate and oleate. Our gene ontology enrichment also showed that palmitate reduces expression of pathways related to protein translation (tRNA acylation, ribonucleoprotein complex biogenesis, etc.). Of especial interest, exposure to palmitate upregulates ER to Golgi mediated transport pathways that could be relevant to insulin secretion. Palmitate exposure also increases many fatty acid metabolism related gene groups. Using thymidine incorporation, we show that at 24 hours proliferation is decreased in beta cells treated with palmitate, but not oleate. We also show the effect of palmitate or oleate exposure on proliferation at 48, 72, and 96 hours of exposure. Using the SUnSET assay, we show the effect of palmitate or oleate exposure on beta cell protein translation. We show the effect of palmitate or oleate exposure on beta cell fatty acid oxidation. Our data shed important light on the specific effects of these fatty acids on beta cells under diabetic conditions. 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.