Glucose-stimulated insulin secretion correlates with β-cell lipolysis

Background and aimsLipids are needed for optimal glucose-stimulated insulin secretion (GSIS), and long-chain acyl-CoA (LC-CoA) has been suggested as one candidate molecule active as a lipidic coupling factor. LC-CoAs may be available to the β-cell via uptake of circulating free fatty acids or from hydrolysis of intracellularly stored triglycerides. Inhibition of lipolysis in rat islets using a non-specific lipase inhibitor (orlistat) resulted in blunted GSIS. The aim of this study was to investigate the relationship between GSIS and lipolysis in clonal β-cells and in mouse islets.Methods and resultsINS-1 cells, cultured overnight at 3.3 mM or 11.1 mM glucose, or freshly isolated islets were incubated with 3.3 mM or 16.7 mM glucose for 1 h. Medium samples were collected and analyzed for insulin and glycerol. Triglycerides were measured in both INS-1 cells and islets. There was a dose-dependent glucose-stimulated lipolysis in INS-1 cells, which strongly correlated with insulin secretion (r = 0.85, P < 0.0001). The same phenomenon was observed in mouse islets (r = 0.9, P = 0.013). Low levels of triglycerides, which were observed in INS-1 cells pre-cultured at 3.3 mM glucose, were associated with reduced GSIS.ConclusionsThis study suggests that lipids obtained from lipolysis of intracellular triglycerides are involved in GSIS.