Differential effects of cis and trans fatty acids on insulin release from isolated mouse islets

In vitro and in vivo studies in animals have shown that elevated levels of free fatty acids (FFAs) induce impaired p-cell function corresponding to th e abnormalities observed in non-insulin-dependent diabetes mellitus (NIDDM) , Previously, it was demonstrated that the chain length and degree of unsat uration are of importance for the insulinotropic effect of fatty acids. How ever, it is not known if the spatial configuration of the fatty acid influe nces beta-cell function. The present study examines whether cis and trans f atty acids acutely influence insulin release and glucose oxidation in isola ted mouse islets in the same way and to the same extent. Thus, we studied t he impact of both cis and transforms of C 18:1 fatty acids. We found that c is and trans vaccenic acid (cis and trans C 18:1 hill, as well as oleic aci d (cis C 18:1 Delta 9) and elaidic acid (trans 18:1 Delta 9), caused a dose -dependent increase in glucose (16.7 mmol/L)-stimulated insulin secretion d uring static islet incubations. The maximal stimulatory effect for cis and trans vaccenic acid and for oleic and elaidic acid was observed at concentr ations of 2.0 and 3.0 mmol/L, respectively. The trans isomers, trans vaccen ic and elaidic acid, elicited a higher maximal insulin output than the resp ective cis isomers, cis vaccenic a nd oleic acid. In the presence of anothe r insulin secretagogue, L-leucine, trans vaccenic but not elaidic acid caus ed a higher response than their cis isomeric fatty acids. The higher potenc y of trans fatty acids compared with the cis forms was confirmed in perifus ion experiments. Both cis and trans C 18:1 fatty acids stimulated insulin s ecretion in a glucose-dependent manner. Also, glucose oxidation was influen ced differentially by the isomers of fatty acids. Glucose oxidation at 16.7 mmol/L glucose was significantly inhibited by oleic and cis vaccenic acid compared with elaidic and trans vaccenic acid, respectively. In summary, ou r results demonstrate that the fatty acid spatial configuration modulates g lucose oxidation and insulin secretion in mouse beta cells. Copyright (C) 1 999 by W.B. Saunders Company.