Secretory, Biosynthetic, Respiratory, Cationic, and Metabolic Responses of Pancreatic Islets to Palmitate and Oleate

Abstract

Palmitate and oleate (0.5 to 1.0 mM) caused a time-and concentration-related augmentation of insulin release evoked by D-glucose (6.0 to 16.7 mM) in rat isolated pancreatic islets. This contrasted with an inhibitory action of the fatty acids upon L-[4-³H] phenylalanine incorporation into TCA-precipitable material, but coincided with an increased biosynthesis of proinsulin relative to that of other islet peptides. The failure of palmitate to cause an immediate increase in insulin output at a low glucose concentration (6.0 mM) coincided with an unchanged rate of O₂ uptake over a 10- to 15-min exposure to this fatty acid. Over prolonged incubation (90 min), however, both palmitate and oleate (1.0 mM) stimulated ⁴⁵Ca net uptake by islets exposed to 6.0 mM D-glucose. Like their insulinotropic effect, the time course for the oxidation of [U-¹⁴C]palmitate and [U-¹⁴C]oleate was characterized by a progressive buildup in ¹⁴CO₂, production rate. Moreover, palmitate and oleate decreased D-[5-³H]glucose conversion to ³HOH and D-[U-¹⁴C]glucose conversion to radioactive acidic metabolites over short (30 min) but not prolonged (120 min) incubation periods. The two fatty acids also interfered with the generation of ¹⁴CO₂, from islets prelabeled with [U-¹⁴C]palmitate, but not L-[U-¹⁴C]glutamine. It is concluded that, at least during prolonged exposure to either palmitate or oleate, the secretory, cationic, and metabolic response to these fatty acids displays features comparable to those usually found in islets stimulated by nutrient secretagogues.