Effects of fatty acids on insulin secretion

Abstract

Caveolin‐1 and cdc42 are involved in insulin granule fusion at the membrane. Normally, caveolin‐1 binds cdc42 and acts as a guanylyl nucleotide inhibitor thereby preventing insulin granule fusion. Glucose stimulates the release of caveolin‐1 from cdc42 allowing insulin granules to fuse with the plasma membrane. Fatty acids prevent the secretion of insulin. The goal of this study is to determine if fatty acids alter the interaction of caveolin‐1 and cdc42. MIN6 cells, a murine pancreatic insulinoma cell line, were treated with 10 μM stearic, linoleic, or palmitic acid for 10 min. In addition, another set of cells were treated with the fatty acids and 20 mM glucose for 10 min. The cells were then immunostained for caveolin‐1, cdc42 and insulin and visualized by immunofluorescence. In untreated cells, caveolin‐1, cdc42, and insulin co‐localized on vesicles. Treatment with glucose caused a decrease in insulin signal and caveolin‐1 and cdc42 no longer co‐localized. In the presence of linoleic or palmitic acid, caveolin‐1 and cdc42 co‐localized and glucose stimulated insulin secretion was inhibited. In the presence of stearic acid, caveolin‐1 and cdc2 did not co‐localize and glucose stimulated insulin release. These data show that palmitic and linoleic acid prevent insulin release by allowing caveolin‐1 to remain bound to cdc42 whereas stearic acid does not interfere with glucose stimulate insulin secretion.