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Published in: Diabetologia 2/2007

01-02-2007 | Article

Exercise training reduces fatty acid availability and improves the insulin sensitivity of glucose metabolism

Authors: F. Shojaee-Moradie, K. C. R. Baynes, C. Pentecost, J. D. Bell, E. L. Thomas, N. C. Jackson, M. Stolinski, M. Whyte, D. Lovell, S. B. Bowes, J. Gibney, R. H. Jones, A. M. Umpleby

Published in: Diabetologia | Issue 2/2007

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Abstract

Aims/hypothesis

It is not known whether the beneficial effects of exercise training on insulin sensitivity are due to changes in hepatic and peripheral insulin sensitivity or whether the changes in insulin sensitivity can be explained by adaptive changes in fatty acid metabolism, changes in visceral fat or changes in liver and muscle triacylglycerol content. We investigated the effects of 6 weeks of supervised exercise in sedentary men on these variables.

Subjects and methods

We randomised 17 sedentary overweight male subjects (age 50 ± 2.6 years, BMI 27.6 ± 0.5 kg/m2) to a 6-week exercise programme (n = 10) or control group (n = 7). The insulin sensitivity of palmitic acid production rate (Ra), glycerol Ra, endogenous glucose Ra (EGP), glucose uptake and glucose metabolic clearance rate were measured at 0 and 6 weeks with a two-step hyperinsulinaemic–euglycaemic clamp [step 1, 0.3 (low dose); step 2, 1.5 (high dose) mU kg−1 min−1]. In the exercise group subjects were studied >72 h after the last training session. Liver and skeletal muscle triacylglycerol content was measured by magnetic resonance spectroscopy and visceral adipose tissue by cross-sectional computer tomography scanning.

Results

After 6 weeks, fasting glycerol, palmitic acid Ra (p = 0.003, p = 0.042) and NEFA concentration (p = 0.005) were decreased in the exercise group with no change in the control group. The effects of low-dose insulin on EGP and of high-dose insulin on glucose uptake and metabolic clearance rate were enhanced in the exercise group but not in the control group (p = 0.026; p = 0.007 and p = 0.04). There was no change in muscle triacylglycerol and liver fat in either group.

Conclusions/interpretation

Decreased availability of circulating NEFA may contribute to the observed improvement in the insulin sensitivity of EGP and glucose uptake following 6 weeks of moderate exercise.
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Literature
1.
go back to reference Ruderman N, Chisholm D, Pi-Sunyer X, Schneider S (1998) The metabolically obese, normal-weight individual revisited. Diabetes 47:699–713PubMed Ruderman N, Chisholm D, Pi-Sunyer X, Schneider S (1998) The metabolically obese, normal-weight individual revisited. Diabetes 47:699–713PubMed
2.
go back to reference Nielsen S, Guo Z, Johnson CM, Hensrud DD, Jensen MD (2004) Splanchnic lipolysis in human obesity. J Clin Invest 113:1582–1588PubMedPubMedCentral Nielsen S, Guo Z, Johnson CM, Hensrud DD, Jensen MD (2004) Splanchnic lipolysis in human obesity. J Clin Invest 113:1582–1588PubMedPubMedCentral
3.
go back to reference Horowitz JF, Coppack SW, Klein S (2001) Whole-body and adipose tissue glucose metabolism in response to short-term fasting in lean and obese women. Am J Clin Nutr 73:517–522PubMed Horowitz JF, Coppack SW, Klein S (2001) Whole-body and adipose tissue glucose metabolism in response to short-term fasting in lean and obese women. Am J Clin Nutr 73:517–522PubMed
4.
go back to reference Jensen MD, Haymond MW, Rizza RA, Cryer PE, Miles JM (1989) Influence of body fat distribution on free fatty acid metabolism in obesity. J Clin Invest 83:1168–1173PubMedPubMedCentral Jensen MD, Haymond MW, Rizza RA, Cryer PE, Miles JM (1989) Influence of body fat distribution on free fatty acid metabolism in obesity. J Clin Invest 83:1168–1173PubMedPubMedCentral
5.
go back to reference Boden G (1998) Free fatty acids (FFA), a link between obesity and insulin resistance. Front Biosci 3:D169–D175PubMed Boden G (1998) Free fatty acids (FFA), a link between obesity and insulin resistance. Front Biosci 3:D169–D175PubMed
6.
go back to reference Randle PJ, Garland PB, Hales CN, Newsholme EA (1963) The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1:785–789PubMed Randle PJ, Garland PB, Hales CN, Newsholme EA (1963) The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1:785–789PubMed
7.
go back to reference Roden M, Krssak M, Stingl H et al (1999) Rapid impairment of skeletal muscle glucose transport/phosphorylation by free fatty acids in humans. Diabetes 48:358–364PubMed Roden M, Krssak M, Stingl H et al (1999) Rapid impairment of skeletal muscle glucose transport/phosphorylation by free fatty acids in humans. Diabetes 48:358–364PubMed
8.
go back to reference Dresner A, Laurent D, Marcucci M et al (1999) Effects of free fatty acids on glucose transport and IRS-1-associated phosphatidylinositol 3-kinase activity. J Clin Invest 103:253–259PubMedPubMedCentral Dresner A, Laurent D, Marcucci M et al (1999) Effects of free fatty acids on glucose transport and IRS-1-associated phosphatidylinositol 3-kinase activity. J Clin Invest 103:253–259PubMedPubMedCentral
9.
go back to reference Wiesenthal SR, Sandhu H, McCall RH et al (1999) Free fatty acids impair hepatic insulin extraction in vivo. Diabetes 48:766–774PubMed Wiesenthal SR, Sandhu H, McCall RH et al (1999) Free fatty acids impair hepatic insulin extraction in vivo. Diabetes 48:766–774PubMed
10.
go back to reference Griffin ME, Marcucci MJ, Cline GW et al (1999) Free fatty acid-induced insulin resistance is associated with activation of protein kinase C theta and alterations in the insulin signalling cascade. Diabetes 48:1270–1274PubMed Griffin ME, Marcucci MJ, Cline GW et al (1999) Free fatty acid-induced insulin resistance is associated with activation of protein kinase C theta and alterations in the insulin signalling cascade. Diabetes 48:1270–1274PubMed
11.
go back to reference Stein DT, Esser V, Stevenson BE et al (1996) Essentiality of circulating fatty acids for glucose-stimulated insulin secretion in the fasted rat. J Clin Invest 97:2728–2735PubMedPubMedCentral Stein DT, Esser V, Stevenson BE et al (1996) Essentiality of circulating fatty acids for glucose-stimulated insulin secretion in the fasted rat. J Clin Invest 97:2728–2735PubMedPubMedCentral
12.
go back to reference Virkamaki A, Korsheninnikova E, Seppala-Lindroos A et al (2001) Intramyocellular lipid is associated with resistance to in vivo insulin actions on glucose uptake, antilipolysis, and early insulin signaling pathways in human skeletal muscle. Diabetes 50:2337–2343PubMed Virkamaki A, Korsheninnikova E, Seppala-Lindroos A et al (2001) Intramyocellular lipid is associated with resistance to in vivo insulin actions on glucose uptake, antilipolysis, and early insulin signaling pathways in human skeletal muscle. Diabetes 50:2337–2343PubMed
13.
go back to reference Seppala-Lindroos A, Vehkavaara S, Hakkinen AM et al (2002) Fat accumulation in the liver is associated with defects in insulin suppression of glucose production and serum free fatty acids independent of obesity in normal men. J Clin Endocrinol Metab 87:3023–3028PubMed Seppala-Lindroos A, Vehkavaara S, Hakkinen AM et al (2002) Fat accumulation in the liver is associated with defects in insulin suppression of glucose production and serum free fatty acids independent of obesity in normal men. J Clin Endocrinol Metab 87:3023–3028PubMed
14.
go back to reference Perseghin G, Price TB, Petersen KF et al (1996) Increased glucose transport-phosphorylation and muscle glycogen synthesis after exercise training in insulin-resistant subjects. N Engl J Med 335:1357–1362PubMed Perseghin G, Price TB, Petersen KF et al (1996) Increased glucose transport-phosphorylation and muscle glycogen synthesis after exercise training in insulin-resistant subjects. N Engl J Med 335:1357–1362PubMed
15.
go back to reference Boden G (1997) Role of fatty acids in the pathogenesis of insulin resistance and NIDDM. Diabetes 46:3–10PubMed Boden G (1997) Role of fatty acids in the pathogenesis of insulin resistance and NIDDM. Diabetes 46:3–10PubMed
16.
go back to reference Meek SE, Nair KS, Jensen MD (1999) Insulin regulation of regional free fatty acid metabolism. Diabetes 48:10–14PubMed Meek SE, Nair KS, Jensen MD (1999) Insulin regulation of regional free fatty acid metabolism. Diabetes 48:10–14PubMed
17.
go back to reference Borg G, Linderholm H (1967) Perceived exertion and pulse rate during graded exercise in various age groups. Acta Med Scand (Suppl) 472:194–206 Borg G, Linderholm H (1967) Perceived exertion and pulse rate during graded exercise in various age groups. Acta Med Scand (Suppl) 472:194–206
18.
go back to reference Eriksson J, Taimela S, Koivisto VA (1997) Exercise and the metabolic syndrome. Diabetologia 40:125–135PubMed Eriksson J, Taimela S, Koivisto VA (1997) Exercise and the metabolic syndrome. Diabetologia 40:125–135PubMed
19.
go back to reference Romijn JA, Coyle EF, Sidossis LS et al (1993) Regulation of endogenous fat and carbohydrate metabolism in relation to exercise intensity and duration. Am J Physiol 265:E380–E391PubMed Romijn JA, Coyle EF, Sidossis LS et al (1993) Regulation of endogenous fat and carbohydrate metabolism in relation to exercise intensity and duration. Am J Physiol 265:E380–E391PubMed
20.
go back to reference Gibney J, Healy ML, Stolinski M et al (2003) Effect of growth hormone (GH) on glycerol and free fatty acid metabolism during exhaustive exercise in GH-deficient adults. J Clin Endocrinol Metab 88:1792–1797PubMed Gibney J, Healy ML, Stolinski M et al (2003) Effect of growth hormone (GH) on glycerol and free fatty acid metabolism during exhaustive exercise in GH-deficient adults. J Clin Endocrinol Metab 88:1792–1797PubMed
21.
go back to reference Brackenridge A, Pearson ER, Shojaee-Moradie F, Hattersley AT, Russell-Jones D, Umpleby AM (2006) Contrasting insulin sensitivity of endogenous glucose production rate in subjects with hepatocyte nuclear factor-1beta and-1alpha mutations. Diabetes 55:405–411PubMed Brackenridge A, Pearson ER, Shojaee-Moradie F, Hattersley AT, Russell-Jones D, Umpleby AM (2006) Contrasting insulin sensitivity of endogenous glucose production rate in subjects with hepatocyte nuclear factor-1beta and-1alpha mutations. Diabetes 55:405–411PubMed
22.
go back to reference Rico-Sanz J, Hajnal JV, Thomas EL, Mierisova S, Ala-Korpela M, Bell JD (1998) Intracellular and extracellular skeletal muscle triglyceride metabolism during alternating intensity exercise in humans. J Physiol 510:615–622PubMedPubMedCentral Rico-Sanz J, Hajnal JV, Thomas EL, Mierisova S, Ala-Korpela M, Bell JD (1998) Intracellular and extracellular skeletal muscle triglyceride metabolism during alternating intensity exercise in humans. J Physiol 510:615–622PubMedPubMedCentral
23.
go back to reference Rico-Sanz J, Thomas EL, Jenkinson G, Mierisova S, Iles R, Bell JD (1999) Diversity in levels of intracellular total creatine and triglycerides in human skeletal muscles observed by (1)H-MRS. J Appl Physiol 87:2068–2072PubMed Rico-Sanz J, Thomas EL, Jenkinson G, Mierisova S, Iles R, Bell JD (1999) Diversity in levels of intracellular total creatine and triglycerides in human skeletal muscles observed by (1)H-MRS. J Appl Physiol 87:2068–2072PubMed
24.
go back to reference Szczepaniak LS, Nurenberg P, Leonard D et al (2005) Magnetic resonance spectroscopy to measure hepatic triglyceride content: prevalence of hepatic steatosis in the general population. Am J Physiol Endocrinol Metab 288:E462–E468PubMed Szczepaniak LS, Nurenberg P, Leonard D et al (2005) Magnetic resonance spectroscopy to measure hepatic triglyceride content: prevalence of hepatic steatosis in the general population. Am J Physiol Endocrinol Metab 288:E462–E468PubMed
25.
go back to reference Rendell M, Hulthen UL, Tornquist C, Groop L, Mattiasson I (2001) Relationship between abdominal fat compartments and glucose and lipid metabolism in early postmenopausal women. J Clin Endocrinol Metab 86:744–749PubMed Rendell M, Hulthen UL, Tornquist C, Groop L, Mattiasson I (2001) Relationship between abdominal fat compartments and glucose and lipid metabolism in early postmenopausal women. J Clin Endocrinol Metab 86:744–749PubMed
26.
go back to reference Shojaee-Moradie F, Jackson NC, Jones RH, Mallet AI, Hovorka R, Umpleby AM (1996) Quantitative measurement of 3-O-methyl-d-glucose by gas chromatography-mass spectrometry as a measure of glucose transport in vivo. J Mass Spectrom 31:961–966PubMed Shojaee-Moradie F, Jackson NC, Jones RH, Mallet AI, Hovorka R, Umpleby AM (1996) Quantitative measurement of 3-O-methyl-d-glucose by gas chromatography-mass spectrometry as a measure of glucose transport in vivo. J Mass Spectrom 31:961–966PubMed
27.
go back to reference Sonksen PH (1976) Double antibody technique for the simultaneous assay of insulin and growth hormone. In: Antoniades HN (ed) Hormones in human blood: detection and assay. Harvard University Press, Cambridge, MA, pp 176–199 Sonksen PH (1976) Double antibody technique for the simultaneous assay of insulin and growth hormone. In: Antoniades HN (ed) Hormones in human blood: detection and assay. Harvard University Press, Cambridge, MA, pp 176–199
28.
go back to reference Steele R, Bishop JS, Dunn A, Altszuler N, Rathbeb I, Debodo RC (1965) Inhjbition by insulin of hepatic glucose production in the normal dog. Am J Physiol 208:301–306PubMed Steele R, Bishop JS, Dunn A, Altszuler N, Rathbeb I, Debodo RC (1965) Inhjbition by insulin of hepatic glucose production in the normal dog. Am J Physiol 208:301–306PubMed
29.
go back to reference Finegood DT, Bergman RN, Vranic M (1987) Estimation of endogenous glucose production during hyperinsulinemic–euglycemic glucose clamps. Comparison of unlabeled and labeled exogenous glucose infusates. Diabetes 36:914–924PubMed Finegood DT, Bergman RN, Vranic M (1987) Estimation of endogenous glucose production during hyperinsulinemic–euglycemic glucose clamps. Comparison of unlabeled and labeled exogenous glucose infusates. Diabetes 36:914–924PubMed
30.
go back to reference Finegood DT, Bergman RN (1983) Optimal segments: a method for smoothing tracer data to calculate metabolic fluxes. Am J Physiol 244:E472–E479PubMed Finegood DT, Bergman RN (1983) Optimal segments: a method for smoothing tracer data to calculate metabolic fluxes. Am J Physiol 244:E472–E479PubMed
31.
go back to reference DeFronzo RA, Sherwin RS, Kraemer N (1987) Effect of physical training on insulin action in obesity. Diabetes 36:1379–1385PubMed DeFronzo RA, Sherwin RS, Kraemer N (1987) Effect of physical training on insulin action in obesity. Diabetes 36:1379–1385PubMed
32.
go back to reference Eriksson J, Taimela S, Koivisto VA (1997) Exercise and the metabolic syndrome. Diabetologia 40:125–135PubMed Eriksson J, Taimela S, Koivisto VA (1997) Exercise and the metabolic syndrome. Diabetologia 40:125–135PubMed
33.
go back to reference DiPietro L, Dziura J, Yeckel CW, Neufer PD (2006) Exercise and improved insulin sensitivity in older women: evidence of the enduring benefits of higher intensity training. J Appl Physiol 100:142–149PubMed DiPietro L, Dziura J, Yeckel CW, Neufer PD (2006) Exercise and improved insulin sensitivity in older women: evidence of the enduring benefits of higher intensity training. J Appl Physiol 100:142–149PubMed
34.
go back to reference Hughes VA, Fiatarone MA, Fielding RA et al (1993) Exercise increases muscle GLUT-4 levels and insulin action in subjects with impaired glucose tolerance. Am J Physiol 264:E855–E862PubMed Hughes VA, Fiatarone MA, Fielding RA et al (1993) Exercise increases muscle GLUT-4 levels and insulin action in subjects with impaired glucose tolerance. Am J Physiol 264:E855–E862PubMed
35.
go back to reference Eckel RH, Yost TJ, Jensen DR (1995) Alterations in lipoprotein lipase in insulin resistance. Int J Obes Relat Metab Disord 19(Suppl 1):S16–S21PubMed Eckel RH, Yost TJ, Jensen DR (1995) Alterations in lipoprotein lipase in insulin resistance. Int J Obes Relat Metab Disord 19(Suppl 1):S16–S21PubMed
36.
go back to reference Miyashita Y, Ebisuno M, Ohhira M et al (2006) Enhancement of serum lipoprotein lipase mass levels by intensive insulin therapy. Diabetes Res Clin Pract 72:61–67PubMed Miyashita Y, Ebisuno M, Ohhira M et al (2006) Enhancement of serum lipoprotein lipase mass levels by intensive insulin therapy. Diabetes Res Clin Pract 72:61–67PubMed
37.
go back to reference De Glisezinski I, Crampes F, Harant I et al (1998) Endurance training changes in lipolytic responsiveness of obese adipose tissue. Am J Physiol 275:E951–E956PubMed De Glisezinski I, Crampes F, Harant I et al (1998) Endurance training changes in lipolytic responsiveness of obese adipose tissue. Am J Physiol 275:E951–E956PubMed
38.
go back to reference Bevilacqua S, Bonadonna R, Buzzigoli G et al (1987) Acute elevation of free fatty acid levels leads to hepatic insulin resistance in obese subjects. Metabolism 36:502–506PubMed Bevilacqua S, Bonadonna R, Buzzigoli G et al (1987) Acute elevation of free fatty acid levels leads to hepatic insulin resistance in obese subjects. Metabolism 36:502–506PubMed
39.
go back to reference Saloranta C, Franssila-Kallunki A, Ekstrand A, Taskinen MR, Groop L (1991) Modulation of hepatic glucose production by non-esterified fatty acids in type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 34:409–415PubMed Saloranta C, Franssila-Kallunki A, Ekstrand A, Taskinen MR, Groop L (1991) Modulation of hepatic glucose production by non-esterified fatty acids in type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 34:409–415PubMed
40.
go back to reference Svedberg J, Bjorntorp P, Smith U, Lonnroth P (1990) Free-fatty acid inhibition of insulin binding, degradation, and action in isolated rat hepatocytes. Diabetes 39:570–574PubMed Svedberg J, Bjorntorp P, Smith U, Lonnroth P (1990) Free-fatty acid inhibition of insulin binding, degradation, and action in isolated rat hepatocytes. Diabetes 39:570–574PubMed
41.
go back to reference Krebs M, Krssak M, Nowotny P et al (2001) Free fatty acids inhibit the glucose-stimulated increase of intramuscular glucose-6-phosphate concentration in humans. J Clin Endocrinol Metab 86:2153–2160PubMed Krebs M, Krssak M, Nowotny P et al (2001) Free fatty acids inhibit the glucose-stimulated increase of intramuscular glucose-6-phosphate concentration in humans. J Clin Endocrinol Metab 86:2153–2160PubMed
42.
go back to reference Santomauro AT, Boden G, Silva ME et al (1999) Overnight lowering of free fatty acids with Acipimox improves insulin resistance and glucose tolerance in obese diabetic and nondiabetic subjects. Diabetes 48:1836–1841PubMed Santomauro AT, Boden G, Silva ME et al (1999) Overnight lowering of free fatty acids with Acipimox improves insulin resistance and glucose tolerance in obese diabetic and nondiabetic subjects. Diabetes 48:1836–1841PubMed
43.
go back to reference Ryysy L, Hakkinen AM, Goto T et al (2000) Hepatic fat content and insulin action on free fatty acids and glucose metabolism rather than insulin absorption are associated with insulin requirements during insulin therapy in type 2 diabetic patients. Diabetes 49:749–758PubMed Ryysy L, Hakkinen AM, Goto T et al (2000) Hepatic fat content and insulin action on free fatty acids and glucose metabolism rather than insulin absorption are associated with insulin requirements during insulin therapy in type 2 diabetic patients. Diabetes 49:749–758PubMed
44.
go back to reference Kelley DE, McKolanis TM, Hegazi RA, Kuller LH, Kalhan SC (2003) Fatty liver in type 2 diabetes mellitus: relation to regional adiposity, fatty acids, and insulin resistance. Am J Physiol Endocrinol Metab 285:E906–E916PubMed Kelley DE, McKolanis TM, Hegazi RA, Kuller LH, Kalhan SC (2003) Fatty liver in type 2 diabetes mellitus: relation to regional adiposity, fatty acids, and insulin resistance. Am J Physiol Endocrinol Metab 285:E906–E916PubMed
45.
go back to reference Frost GS, Goff LM, Hamilton G et al (2003) Carbohydrate-induced manipulation of insulin sensitivity independently of intramyocellular lipids. Br J Nutr 89:365–375PubMed Frost GS, Goff LM, Hamilton G et al (2003) Carbohydrate-induced manipulation of insulin sensitivity independently of intramyocellular lipids. Br J Nutr 89:365–375PubMed
Metadata
Title
Exercise training reduces fatty acid availability and improves the insulin sensitivity of glucose metabolism
Authors
F. Shojaee-Moradie
K. C. R. Baynes
C. Pentecost
J. D. Bell
E. L. Thomas
N. C. Jackson
M. Stolinski
M. Whyte
D. Lovell
S. B. Bowes
J. Gibney
R. H. Jones
A. M. Umpleby
Publication date
01-02-2007
Publisher
Springer Berlin Heidelberg
Published in
Diabetologia / Issue 2/2007
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-006-0498-7

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