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01-04-2014 | Research Article

Relationship of muscle sympathetic nerve activity to insulin sensitivity

Authors: Timothy B. Curry, Casey N. Hines, Jill N. Barnes, Madhuri Somaraju, Rita Basu, John M. Miles, Michael J. Joyner, Nisha Charkoudian

Published in: Clinical Autonomic Research | Issue 2/2014

Abstract

Purpose

An association between insulin resistance and activation of the sympathetic nervous system has been reported in previous studies. However, potential interactions between insulin sensitivity and sympathetic neural mechanisms in healthy people remain poorly understood. We conducted a study to determine the relationship between sympathetic activity and insulin resistance in young, healthy humans.

Methods

Thirty-seven healthy adults (18–35 years, BMI <28 kg m⁻²) were studied. Resting muscle sympathetic nerve activity (MSNA) was measured with microneurography and insulin sensitivity of glucose and free fatty acid metabolism was measured during a hyperinsulinemic-euglycemic clamp with two levels of insulin.

Results

During lower doses of insulin, we found a small association between lower insulin sensitivity and higher MSNA (P < 0.05) but age was a cofactor in this relationship. Overall, we found no difference in insulin sensitivity between groups of low and high MSNA, but when women were analyzed separately, insulin sensitivity was lower in the high MSNA group compared with the low MSNA group of women.

Conclusions

These data suggest that MSNA and insulin sensitivity are only weakly associated with young healthy individuals and that age and sex may be important modifiers of this relationship.

Boden G, Chen X, Ruiz J, White JV, Rossetti L (1994) Mechanisms of fatty acid-induced inhibition of glucose uptake. J Clin Invest 93:2438–2446PubMedCentralPubMedCrossRef

Charkoudian N, Joyner MJ, Sokolnicki LA, Johnson CP, Eisenach JH, Dietz NM, Curry TB, Wallin BG (2006) Vascular adrenergic responsiveness is inversely related to tonic activity of sympathetic vasoconstrictor nerves in humans. J Physiol 572:821–827PubMedCentralPubMedCrossRef

Curry TB, Roberts SK, Basu R, Basu A, Schroeder D, Joyner MJ, Miles JM (2011) Gastric bypass surgery is associated with near-normal insulin suppression of lipolysis in nondiabetic individuals. Am J Physiol Endocrinol Metab 300:E746–E751PubMedCentralPubMedCrossRef

Facchini FS, Stoohs RA, Reaven GM (1996) Enhanced sympathetic nervous system activity. The linchpin between insulin resistance, hyperinsulinemia, and heart rate. Am J Hypertens 9:1013–1017PubMedCrossRef

Flaa A, Aksnes TA, Kjeldsen SE, Eide I, Rostrup M (2008) Increased sympathetic reactivity may predict insulin resistance: an 18-year follow-up study. Metabolism 57:1422–1427PubMedCrossRef

Flanagan DE, Vaile JC, Petley GW, Moore VM, Godsland IF, Cockington RA, Robinson JS, Phillips DI (1999) The autonomic control of heart rate and insulin resistance in young adults. J Clin Endocr Metab 84:1263–1267PubMed

Florian JP, Pawelczyk JA (2009) Non-esterified fatty acids increase arterial pressure via central sympathetic activation in humans. Clin Sci (Colch) 118:61–69CrossRef

Geer EB, Shen W (2009) Gender differences in insulin resistance, body composition, and energy balance. Gend Med 6(Suppl 1):60–75PubMedCentralPubMedCrossRef

Grassi G, Dell’Oro R, Quarti-Trevano F, Scopelliti F, Seravalle G, Paleari F, Gamba PL, Mancia G (2005) Neuroadrenergic and reflex abnormalities in patients with metabolic syndrome. Diabetologia 48:1359–1365PubMedCrossRef

10.

Grassi G, Seravalle G, Quarti-Trevano F, Mineo C, Lonati L, Facchetti R, Mancia G (2010) Reinforcement of the adrenergic overdrive in the metabolic syndrome complicated by obstructive sleep apnea. J Hypertens 28:1313–1320PubMed

11.

Gudbjornsdottir S, Friberg P, Elam M, Attvall S, Lonnroth P, Wallin BG (1994) The effect of metformin and insulin on sympathetic nerve activity, norepinephrine spillover and blood pressure in obese, insulin resistant, normoglycemic, hypertensive men. Blood Press 3:394–403PubMedCrossRef

12.

Henry S, Trueb L, Sartori C, Scherrer U, Jequier E, Tappy L (1998) Effects of a sympathetic activation by a lower body negative pressure on glucose and lipid metabolism. Clin Physiol 18:562–569PubMedCrossRef

13.

Huggett RJ, Burns J, Mackintosh AF, Mary DA (2004) Sympathetic neural activation in nondiabetic metabolic syndrome and its further augmentation by hypertension. Hypertension 44:847–852PubMedCrossRef

14.

Huggett RJ, Hogarth AJ, Mackintosh AF, Mary DA (2006) Sympathetic nerve hyperactivity in non-diabetic offspring of patients with type 2 diabetes mellitus. Diabetologia 49:2741–2744PubMedCrossRef

15.

Huggett RJ, Scott EM, Gilbey SG, Stoker JB, Mackintosh AF, Mary DA (2003) Impact of type 2 diabetes mellitus on sympathetic neural mechanisms in hypertension. Circulation 108:3097–3101PubMedCrossRef

16.

Jamerson KA, Julius S, Gudbrandsson T, Andersson O, Brant DO (1993) Reflex sympathetic activation induces acute insulin resistance in the human forearm. Hypertension 21:618–623PubMedCrossRef

17.

Jensen MD, Kanaley JA, Reed JE, Sheedy PF (1995) Measurement of abdominal and visceral fat with computed tomography and dual-energy X-ray absorptiometry. Am J Clin Nutr 61:274–278PubMed

18.

Jones PP, Snitker S, Skinner JS, Ravussin E (1996) Gender differences in muscle sympathetic nerve activity: effect of body fat distribution. Am J Physiol 270:E363–E366PubMed

19.

Julius S, Jamerson K (1994) Sympathetics, insulin resistance and coronary risk in hypertension: the ‘chicken-and-egg’ question. J Hypertens 12:495–502PubMedCrossRef

20.

Khoury N, McGill JB (2011) Reduction in insulin sensitivity following administration of the clinically used low-dose pressor, norepinephrine. Diabetes Metab Res Rev 27:604–608PubMedCentralPubMedCrossRef

21.

Kienbaum P, Karlssonn T, Sverrisdottir YB, Elam M, Wallin BG (2001) Two sites for modulation of human sympathetic activity by arterial baroreceptors? J Physiol (Lond) 531:861–869CrossRef

22.

Klein S (2004) The case of visceral fat: argument for the defense. J Clin Invest 113:1530–1532PubMedCentralPubMedCrossRef

23.

Lambert GW, Straznicky NE, Lambert EA, Dixon JB, Schlaich MP (2010) Sympathetic nervous activation in obesity and the metabolic syndrome—causes, consequences and therapeutic implications. Pharmacol Ther 126:159–172PubMedCrossRef

24.

Masuo K, Mikami H, Ogihara T, Tuck ML (1997) Sympathetic nerve hyperactivity precedes hyperinsulinemia and blood pressure elevation in a young, nonobese Japanese population. Am J Hypertens 10:77–83PubMedCrossRef

25.

McCarty MF (2004) Elevated sympathetic activity may promote insulin resistance syndrome by activating alpha-1 adrenergic receptors on adipocytes. Med Hypotheses 62:830–838PubMedCrossRef

26.

Miles JM, Ellman MG, McClean KL, Jensen MD (1987) Validation of a new method for determination of free fatty acid turnover. Am J Physiol 252:E431–E438PubMed

27.

Miles JM, Nelson RH (2007) Lipid kinetics. In: Roden M (ed) Clinical diabetes research: methods and techniques. Wiley, Chichester, pp 151–168CrossRef

28.

Minson CT, Halliwill JR, Young TM, Joyner MJ (2000) Influence of the menstrual cycle on sympathetic activity, baroreflex sensitivity, and vascular transduction in young women. Circulation 101:862–868PubMedCrossRef

29.

Muntzel MS, Anderson EA, Johnson AK, Mark AL (1995) Mechanisms of insulin action on sympathetic nerve activity. Clin Exp Hypertens 17:39–50PubMedCrossRef

30.

Narkiewicz K, Kato M, Phillips BG, Pesek CA, Choe I, Winnicki M, Palatini P, Sivitz WI, Somers VK (2001) Leptin interacts with heart rate but not sympathetic nerve traffic in healthy male subjects. J Hypertens 19:1089–1094PubMedCrossRef

31.

Narkiewicz K, Winnicki M, Schroeder K, Phillips BG, Kato M, Cwalina E, Somers VK (2002) Relationship between muscle sympathetic nerve activity and diurnal blood pressure profile. Hypertension 39:168–172PubMedCrossRef

32.

Ng AV, Callister R, Johnson DG, Seals DR (1993) Age and gender influence muscle sympathetic nerve activity at rest in healthy humans. Hypertension 21:498–503PubMedCrossRef

33.

Nielsen S, Halliwill JR, Joyner MJ, Jensen MD (2004) Vascular response to angiotensin II in upper body obesity. Hypertension 44:435–441PubMedCrossRef

34.

Scherrer U, Randin D, Tappy L, Vollenweider P, Jequier E, Nicod P (1994) Body fat and sympathetic nerve activity in healthy subjects. Circulation 89:2634–2640PubMedCrossRef

35.

Shadid S, Kanaley JA, Sheehan MT, Jensen MD (2007) Basal and insulin-regulated free fatty acid and glucose metabolism in humans. Am J Physiol Endocrinol Metab 292:E1770–E1774PubMedCrossRef

36.

Straznicky NE, Eikelis N, Lambert EA, Esler MD (2008) Mediators of sympathetic activation in metabolic syndrome obesity. Curr Hypertens Rep 10:440–447PubMedCrossRef

37.

Sundlof G, Wallin BG (1978) Human muscle nerve sympathetic activity at rest. Relationship to blood pressure and age. J Physiol (Lond) 274:621–637

38.

Valdes CT, Elkind-Hirsch KE (1991) Intravenous glucose tolerance test-derived insulin sensitivity changes during the menstrual cycle. J Clin Endocr Metab 72:642–646PubMedCrossRef

39.

Vella A, Shah P, Basu R, Basu A, Camilleri M, Schwenk WF, Rizza RA (2001) Type I diabetes mellitus does not alter initial splanchnic glucose extraction or hepatic UDP-glucose flux during enteral glucose administration. Diabetologia 44:729–737PubMedCrossRef

40.

Wallin BG, Esler M, Dorward P, Eisenhofer G, Ferrier C, Westerman R, Jennings G (1992) Simultaneous measurements of cardiac noradrenaline spillover and sympathetic outflow to skeletal muscle in humans. J Physiol (Lond) 453:45–58

41.

Wallin BG, Sundlof G (1979) A quantitative study of muscle nerve sympathetic activity in resting normotensive and hypertensive subjects. Hypertension 1:67–77PubMedCrossRef

42.

Wallin BG, Thompson JM, Jennings GL, Esler MD (1996) Renal noradrenaline spillover correlates with muscle sympathetic activity in humans. J Physiol (Lond) 491:881–887

43.

Young CN, Deo SH, Chaudhary K, Thyfault JP, Fadel PJ (2010) Insulin enhances the gain of arterial baroreflex control of muscle sympathetic nerve activity in humans. J Physiol (Lond) 588:3593–3603CrossRef

Title: Relationship of muscle sympathetic nerve activity to insulin sensitivity
Authors: Timothy B. Curry
Casey N. Hines
Jill N. Barnes
Madhuri Somaraju
Rita Basu
John M. Miles
Michael J. Joyner
Nisha Charkoudian
Publication date: 01-04-2014
Publisher: Springer Berlin Heidelberg
Published in: Clinical Autonomic Research / Issue 2/2014
Print ISSN: 0959-9851
Electronic ISSN: 1619-1560
DOI: https://doi.org/10.1007/s10286-014-0235-0

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Relationship of muscle sympathetic nerve activity to insulin sensitivity

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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