SECRETORY, BIOSYNTHETIC, RESPIRATORY, CATIONIC, AND METABOLIC RESPONSES OF PANCREATIC-ISLETS TO PALMITATE AND OLEATE

Palmitate and oleate (0.5 to 1.0 mM) caused a time-and concentration-r elated augmentation of insulin release evoked by D-glucose (6.0 to 16. 7 mM) in rat isolated pancreatic islets. This contrasted with an inhib itory action of the fatty acids upon L-[4-H-3] phenylalanine incorpora tion into TCA-precipitable material, but coincided with an increased b iosynthesis of proinsulin relative to that of other islet peptides. Th e failure of palmitate to cause an immediate increase in insulin outpu t at a low glucose concentration (6.0 mM) coincided with an unchanged rate of O-2 uptake over a 10- to 15-min exposure to this fatty acid. O ver prolonged incubation (90 min), however, both palmitate and oleate (1.0 mM) stimulated(45)Ca net uptake by islets exposed to 6.0 mM D-glu cose. Like their insulinotropic effect, the time course for the oxidat ion of [U-C-14]palmitate and [U-C-14]oleate was characterized by a pro gressive buildup in (CO2)-C-14, production rate. Moreover, palmitate a nd oleate decreased D-[5-H-3]glucose conversion to (HOH)-H-3 and D-[U- C-14]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 (CO2)-C-14, from islets p relabeled with [U-C-14]palmitate, but not L-[U-C-14]glutamine. It is c oncluded that, at least during prolonged exposure to either palmitate or oleate, the secretory, cationic, and metabolic response to these fa tty acids displays features comparable to those usually found in islet s stimulated by nutrient secretagogues. (C) 1994 Academic Press, Inc.