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. 1999 Feb;103(3):413-9.
doi: 10.1172/JCI3883.

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

C Magnan  1 , S Collins, M F Berthault, N Kassis, M Vincent, M Gilbert, L Pénicaud, A Ktorza, F Assimacopoulos-Jeannet
Affiliations

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

C Magnan et al. J Clin Invest. 1999 Feb.

Abstract

We investigated the possible involvement of the autonomic nervous system in the effect of a long-term elevation of plasma free fatty acid (FFA) concentration on glucose-induced insulin secretion (GIIS) in rats. Rats were infused 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 (DeltaI/DeltaG) was 2.5-fold greater in IL rats compared with control saline-infused rats. The ratio of sympathetic to parasympathetic nervous activities was sharply decreased in IL rats relative to controls. GIIS was studied in the presence of increasing amounts of alpha- and beta-adrenoreceptor agonists and antagonists. The lowest concentrations of the alpha2A-adrenoreceptor agonist oxymetazoline, which were ineffective in control rats, reduced GIIS in IL rats. 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 (propranolol) 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, indicating that changes in parasympathetic tone were of minor importance. Altogether, the data show that lipid infusion provokes beta-cell hyperresponsiveness in vivo, at least in part through changes in alpha2-adrenergic innervation.

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Figures

Figure 1
Figure 1
Effects of increasing concentrations of glucose on insulin release by freshly isolated islets of control (open circles) and lipids-infused (filled circles) rats. Values are means ± SEM of five cases for both groups. **P < 0.01, ***P < 0.001, significantly different from 5.5 mM glucose.
Figure 2
Figure 2
(a) Fragments of illustrative recordings of parasympathetic (PSNA) and sympathetic (SNA) nerve activity from control (C) and lipids-infused (IL) rats. (b) Parasympathetic and sympathetic activities in control (open bars) and IL (filled bars) rats. Recorded from vagus nerve and superior cervical ganglion, respectively. Values are means ± SEM of five cases for both groups. ***P < 0.001, significantly different from controls. (c) Ratio of sympathetic to parasympathetic nerve activities.
Figure 3
Figure 3
Time course of plasma insulin (a) and glucose (b) concentrations in response to glucose loading in control (open circles) and IL (filled circles) rats. Values are means ± SEM of 10 cases for both groups. (c) Insulinogenic index (ΔI/ΔG) in control (open bar) and IL (filled bar) rats. ***P < 0.001, significantly different from control rats.
Figure 4
Figure 4
Insulinogenic index (ΔI/ΔG) in response to glucose loading in presence of increasing amounts of either oxymetazoline or yohimbine in control (open bars) and IL (filled bars) rats. Values are means ± SEM of six cases for each dose. ***P < 0.001, significantly different from control rats. ++P < 0.05, +++P < 0.001, significantly different from basal value (without oxymetazoline or yohimbine).
Figure 5
Figure 5
Insulinogenic index (ΔI/ΔG) in response to glucose loading in the presence of increasing amounts of isoproterenol (a) or propranolol (b) in control (open bars) and IL (filled bars). Values are means ± SEM of six cases for each dose. ***P < 0.001, significantly different from controls.
Figure 6
Figure 6
Insulinogenic index (ΔI/ΔG) in response to glucose loading in control and lipids-infused rats under subdiaphragmatic vagotomy. Values are means ± SEM of six cases for all groups. ***P < 0.001, significantly different from intact rats. C, control rats; Cv, control vagotomized rats; IL, lipids-infused rats; ILv, lipids-infused vagotomized rats.
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