Autonomic blockade improves insulin sensitivity in obese subjects.

Gamboa A, Okamoto LE, Arnold AC, Figueroa RA, Diedrich A, Raj SR, Paranjape SY, Farley G, Abumrad N, Biaggioni I
Hypertension. 2014 64 (4): 867-74

PMID: 25001269 · PMCID: PMC4162826 · DOI:10.1161/HYPERTENSIONAHA.114.03738

Obesity is an important risk factor for the development of insulin resistance. Initial compensatory mechanisms include an increase in insulin levels, which are thought to induce sympathetic activation in an attempt to restore energy balance. We have previously shown, however, that sympathetic activity has no beneficial effect on resting energy expenditure in obesity. On the contrary, we hypothesize that sympathetic activation contributes to insulin resistance. To test this hypothesis, we determined insulin sensitivity using a standard hyperinsulinemic euglycemic clamp protocol in obese subjects randomly assigned in a crossover design 1 month apart to receive saline (intact day) or trimetaphan (4 mg/min IV, autonomic blocked day). Whole-body glucose uptake (MBW in mg/kg per minute) was used as index of maximal muscle glucose use. During autonomic blockade, we clamped blood pressure with a concomitant titrated intravenous infusion of the nitric oxide synthase inhibitor N-monomethyl-L-arginine. Of the 21 obese subjects (43±2 years; 35±2 kg/m(2) body mass index) studied, 14 were insulin resistant; they were more obese, had higher plasma glucose and insulin, and had higher muscle sympathetic nerve activity (23.3±1.5 versus 17.2±2.1 burst/min; P=0.03) when compared with insulin-sensitive subjects. Glucose use improved during autonomic blockade in insulin-resistant subjects (MBW 3.8±0.3 blocked versus 3.1±0.3 mg/kg per minute intact; P=0.025), with no effect in the insulin-sensitive group. These findings support the concept that sympathetic activation contributes to insulin resistance in obesity and may result in a feedback loop whereby the compensatory increase in insulin levels contributes to greater sympathetic activation.

© 2014 American Heart Association, Inc.

MeSH Terms (19)

Adult Autonomic Nervous System Blood Glucose Blood Pressure Cross-Over Studies Enzyme Inhibitors Female Ganglionic Blockers Glucose Clamp Technique Humans Insulin Insulin Resistance Male Middle Aged Muscles Nitric Oxide Synthase Obesity omega-N-Methylarginine Trimethaphan

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