Autonomic blockade improves insulin sensitivity in obese subjects

Alfredo Gamboa, Luis E. Okamoto, Amy C. Arnold, Rocio A. Figueroa, André Diedrich, Satish R. Raj, Sachin Y. Paranjape, Ginnie Farley, Naji Abumrad, Italo Biaggioni

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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/m2 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.

Original languageEnglish (US)
Pages (from-to)867-874
Number of pages8
JournalHypertension
Volume64
Issue number4
DOIs
StatePublished - Jan 1 2014

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Insulin Resistance
Insulin
Glucose
Obesity
Trimethaphan
Muscles
Glucose Clamp Technique
Intravenous Infusions
Nitric Oxide Synthase
Cross-Over Studies
Energy Metabolism
Arginine
Body Mass Index
Blood Pressure

All Science Journal Classification (ASJC) codes

  • Internal Medicine

Cite this

Gamboa, A., Okamoto, L. E., Arnold, A. C., Figueroa, R. A., Diedrich, A., Raj, S. R., ... Biaggioni, I. (2014). Autonomic blockade improves insulin sensitivity in obese subjects. Hypertension, 64(4), 867-874. https://doi.org/10.1161/HYPERTENSIONAHA.114.03738
Gamboa, Alfredo ; Okamoto, Luis E. ; Arnold, Amy C. ; Figueroa, Rocio A. ; Diedrich, André ; Raj, Satish R. ; Paranjape, Sachin Y. ; Farley, Ginnie ; Abumrad, Naji ; Biaggioni, Italo. / Autonomic blockade improves insulin sensitivity in obese subjects. In: Hypertension. 2014 ; Vol. 64, No. 4. pp. 867-874.
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Gamboa, A, Okamoto, LE, Arnold, AC, Figueroa, RA, Diedrich, A, Raj, SR, Paranjape, SY, Farley, G, Abumrad, N & Biaggioni, I 2014, 'Autonomic blockade improves insulin sensitivity in obese subjects', Hypertension, vol. 64, no. 4, pp. 867-874. https://doi.org/10.1161/HYPERTENSIONAHA.114.03738

Autonomic blockade improves insulin sensitivity in obese subjects. / Gamboa, Alfredo; Okamoto, Luis E.; Arnold, Amy C.; Figueroa, Rocio A.; Diedrich, André; Raj, Satish R.; Paranjape, Sachin Y.; Farley, Ginnie; Abumrad, Naji; Biaggioni, Italo.

In: Hypertension, Vol. 64, No. 4, 01.01.2014, p. 867-874.

Research output: Contribution to journalArticle

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T1 - Autonomic blockade improves insulin sensitivity in obese subjects

AU - Gamboa, Alfredo

AU - Okamoto, Luis E.

AU - Arnold, Amy C.

AU - Figueroa, Rocio A.

AU - Diedrich, André

AU - Raj, Satish R.

AU - Paranjape, Sachin Y.

AU - Farley, Ginnie

AU - Abumrad, Naji

AU - Biaggioni, Italo

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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/m2 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.

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