Lipid infusion lowers sympathetic nervous activity and leads to increased beta-cell responsiveness to glucose

We investigated the possible involvement of the autonomic nervous system in the effect of a long-term elevation of plasma free fatty acid (FFA) concen tration on glucose-induced insulin secretion (GIIS) in rats. Rats were infu sed with an emulsion of triglycerides (Intralipid) for 48 hours (IL rats). This resulted in a twofold increase in plasma FFA concentration. At the end of infusion, GIIS as reflected in the insulinogenic index (Delta I/Delta G ) was 2.5-fold greater in IL rats compared with control saline-infused rats . The ratio of sympathetic to parasympathetic nervous activities was sharpl y decreased in IL rats relative to controls. GIIS was studied in the presen ce of increasing amounts of alpha- and beta-adrenoreceptor agonists and ant agonists. The lowest concentrations of the alpha 2A-adrenoreceptor agonist oxymetazoline, which were ineffective in control rats, reduced GIIS in IL r ats. At the dose of 0.3 pmol/kg, GIIS became similar in IL and control rats . The use of beta-adrenoreceptor agonist (isoproterenol) or antagonist (pro pranolol) did not result in a significant alteration in GIIS in both groups . GIIS remained as high in IL vagotomized rats as in intact IL rats, indica ting that changes in parasympathetic tone were of minor importance. Altoget her, the data show that lipid infusion provokes beta-cell hyperresponsivene ss in vivo, at least in part through changes in alpha 2-adrenergic innervat ion.