Hostname: page-component-586b7cd67f-gb8f7 Total loading time: 0 Render date: 2024-11-23T02:39:43.121Z Has data issue: false hasContentIssue false
  • English
  • Français

Carbohydrate-induced manipulation of insulin sensitivity independently of intramyocellular lipids

Published online by Cambridge University Press:  09 March 2007

Louise M. Goff ,
Gary S. Frost ,
Gavin Hamilton ,
E. Louise Thomas ,
Waljit S. Dhillo ,
Anne Dornhorst  and
Jimmy D. Bell
Louise M. Goff
Affiliation:
MRC MRI Unit, Clinical Sciences Centre, Division of Investigative Science, Hammersmith Hospital, Imperial College School of Medicine, London W12 0HS, UK Department of Nutrition & Dietetics, Division of Investigative Science, Hammersmith Hospital, Imperial College School of Medicine, London W12 0HS, UK
Gary S. Frost*
Affiliation:
Department of Nutrition & Dietetics, Division of Investigative Science, Hammersmith Hospital, Imperial College School of Medicine, London W12 0HS, UK
Gavin Hamilton
Affiliation:
MRC MRI Unit, Clinical Sciences Centre, Division of Investigative Science, Hammersmith Hospital, Imperial College School of Medicine, London W12 0HS, UK
E. Louise Thomas
Affiliation:
MRC MRI Unit, Clinical Sciences Centre, Division of Investigative Science, Hammersmith Hospital, Imperial College School of Medicine, London W12 0HS, UK
Waljit S. Dhillo
Affiliation:
Department of Metabolic Medicine, Division of Investigative Science, Hammersmith Hospital, Imperial College School of Medicine, London W12 0HS, UK
Anne Dornhorst
Affiliation:
Department of Metabolic Medicine, Division of Investigative Science, Hammersmith Hospital, Imperial College School of Medicine, London W12 0HS, UK
Jimmy D. Bell
Affiliation:
MRC MRI Unit, Clinical Sciences Centre, Division of Investigative Science, Hammersmith Hospital, Imperial College School of Medicine, London W12 0HS, UK
*
*Corresponding author: Dr Gary S. Frost, fax +44 20 8383 3379, email [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Subjects with insulin resistance have been shown to have higher storage levels of intramyocellular lipid (IMCL) than their insulin-sensitive counterparts. It has been proposed that elevated IMCL stores may be the main cause of insulin resistance. The aim of the present study was to ascertain whether there is a causal relationship between IMCL storage and insulin resistance. IMCL storage was assessed using magnetic resonance spectroscopy and insulin sensitivity was assessed by performing an oral glucose tolerance test. A 4-week intervention of reduction of dietary glycaemic index was used to manipulate insulin sensitivity in a cohort of healthy volunteers; the effects of this intervention on IMCL were measured after 4 weeks of intervention. Significant improvements in the insulin sensitivity index occurred following the dietary intervention (baseline 7·8 (sem 1·11) v. post-intervention 9·7 (sem 1·11), P=0·02). However, there were no changes in IMCL storage levels, suggesting that insulin sensitivity can be manipulated independently of IMCL. This suggests that in healthy volunteers, insulin sensitivity is independent of IMCL storage and the high storage levels that have been found in insulin-resistant subjects may occur as a consequence rather than a cause of insulin resistance.

Keywords

Intramyocellular lipidsInsulin resistanceInsulin sensitivityMagnetic resonance spectroscopyGlycaemic indexCarbohydrate
Type
Research Article
Information
British Journal of Nutrition , Volume 89 , Issue 3 , March 2003 , pp. 365 - 374
Copyright
Copyright © The Nutrition Society 2003

References

Abel, ED, Peroni, OD, Kim, JK, Kim, Y-B, Boss, O, Hadro, E, Minnemann, T, Shulman, GI & Kahn, BB (2001) Adipose-selective targeting of the GLUT4 gene impairs insulin action in musle and liver. Nature 409, 729–733.CrossRefGoogle Scholar
Albano, JD, Ekins, RP, Maritz, G & Turner, RC (1972) A sensitive, precise radioimmunoassay of serum insulin relying on charcoal separation of bound and free hormone moieties. Acta Endocrinology 70, 487–509.Google ScholarPubMed
Boden, G, Lebed, B, Schatz, M, Homko, C & Lemieux, S (2001) Effects of acute changes of plasma free fatty acids on intramyocellular free fatty acids and insulin resistance in healthy subjects. Diabetes 50, 1612–1617.CrossRefGoogle ScholarPubMed
Brechtel, K, Dahl, DB, Machann, J, Bachmann, OP, Wenzel, I, Maier, T, Claussen, C, Haring, HU, Jacob, S & Schick, F (2001) Fast elevation of the intramyocellular lipid content in the presence of circulating free fatty acids and hyperinsulinemia: A dynamic 1H-MRS study. Magnetic Resonance in Medicine 45, 179–183.3.0.CO;2-D>CrossRefGoogle ScholarPubMed
Daly, ME, Vale, C, Walker, M, Alberti, KG & Mathers, JC (1997) Dietary carbohydrates and insulin sensitivity: a review of the evidence and clinical implications. American Journal of Clinical Nutrition 66, 1072–1085.CrossRefGoogle ScholarPubMed
Department of Health (1991) Dietary Reference Values for Food Energy and Nutrients for the United Kingdom: Report of the Panel on Dietary Reference Committee on Medical Aspects of Food Policy. London: H. M. Stationery Office.Google Scholar
Falholt, K, Jensen, I, Lindkaer, JS, Mortensen, H, Volund, A, Heding, LG, Noerskov, PP & Falholt, W (1988) Carbohydrate and lipid metabolism of skeletal muscle in type 2 diabetic patients. Diabetic Medicine 5, 27–31.CrossRefGoogle ScholarPubMed
Forouhi, NG, Jenkinson, G, Thomas, EL, Mullik, S, Mierisova, S, Bhonsle, SM, Keigue, PM & Bell, JD (1999) Relation of triglyceride stores in skeletal muscle cells to central obesity and insulin sensitivity in European and South Asian men. Diabetologia 42, 932–935.CrossRefGoogle ScholarPubMed
Foster, PK & Miller, JB (1995) International tables of glycemic index. American Journal of Clinical Nutrition 62, 871S–890S.CrossRefGoogle Scholar
Frost, G, Keogh, B, Smith, D, Akinsanya, K & Leeds, A (1996) The effect of low-glycemic carbohydrate on insulin and glucose response in vivo and in vitro in patients with coronary heart disease. Metabolism 45, 669–672.CrossRefGoogle ScholarPubMed
Frost, G, Leeds, A, Dore, C, Madeiros, S, Brading, S & Dornhorst, A (1999) Glycaemic index as a determinant of serum HDL-cholesterol concentration. Lancet 353, 1045–1048.CrossRefGoogle ScholarPubMed
Frost, G, Leeds, A, Trew, G, Margara, R & Dornhorst, A (1998) Insulin sensitivity in women at risk of coronary heart disease and the effect of a low glycaemic diet. Metabolism 47, 1245–1251.CrossRefGoogle Scholar
Furler, SM, Poynten, A, Kriketos, AD, Lowy, AJ, Ellis, BA, Maclean, EL, Courtenay, BG, Kraegen, EW, Campbell, LV & Chisholm, DJ (2001) Independent influences of central fat and skeletal muscle lipids on insulin sensitivity. Obesity Research 9, 535–543.CrossRefGoogle ScholarPubMed
Goodpaster, BH, He, J, Watkins, S & Kelley, DE (2001) Skeletal muscle lipid content and insulin resistance: evidence for a paradox in endurance-trained athletes. Journal of Clinical Endocrinology and Metabolism 86, 5755–5761.CrossRefGoogle ScholarPubMed
Goodpaster, BH, Theriault, R, Watkins, SC & Kelley, DE (2000) Intramusular lipid content is increased in obesity and decreased by weight loss. Metabolism 49, 467–472.CrossRefGoogle ScholarPubMed
Jacob, S, Machann, J, Rett, K, Brechtel, K, Volk, A, Renn, W, Maerker, E, Matthaei, S, Schick, F, Claussen, C & Haring, H (1999) Association of increased myocellular lipid content with insulin resistance in lean nondiabetic offspring of type II diabetic subjects. Diabetes 48, 1113–1119.CrossRefGoogle Scholar
Jenkins, DJ, Wolever, TM, Buckley, G, Lam, KY, Giudici, S, Kalmusky, J, Jenkins, AL, Patten, RL, Bird, J, Wong, GS & Josse, RG (1988) Low-glycemic-index starchy foods in the diabetic diet. American Journal of Clinical Nutrition 48, 248–254.CrossRefGoogle ScholarPubMed
Koyama, K, Chen, G, Lee, Y & Unger, RH (1997) Tissue triglycerides insulin resistance and insulin production: implications for hyperinsulinemia of obesity. American Journal of Physiology 273, E708–E713.Google ScholarPubMed
Kraegen, EW, Clark, PW, Jenkins, AB, Daley, EA, Chisholm, DJ & Storlien, LH (1991) Development of muscle insulin resistance after liver insulin resistance in high-fat-fed rats. Diabetes 40, 1397–1403.CrossRefGoogle ScholarPubMed
Krssak, M, Krebs, M, Stingl, H, Mlynarik, V, Gruber, S, Moser, E & Roden, M (2000) Intramyocellular lipid (IMCL) stores before and after lipid infusion. Proceedings of the International Society for Magnetic Resonance in Medicine 8, Abstr.Google Scholar
Krssak, M, Petersen, KF, Dresner, A, DiPietro, L, Vogel, SM, Rothman, DL, Shulman, GI & Roden, M (1999) Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: an H-1 NMR spectroscopy study. Diabetologia 42, 113–116.CrossRefGoogle Scholar
Laybutt, DR, Chisholm, DJ & Kraegen, EW (1997) Specific adaptations in muscle and adipose tissue in response to chronic systemic glucose oversupply in rats. American Journal of Physiology 273, E1–E9.Google ScholarPubMed
Liu, S, Willett, W, Stampfer, MJ, Hu, FB, Franz, M, Sampson, L, Hennekens, CH & Manson, JE (2000) A prospective study of dietary glycemic load carbohydrate intake and risk of coronary heart disease in US women.. American Journal of Clinical Nutrition 71, 1455–1461 Abstr.CrossRefGoogle ScholarPubMed
Magnetic Resonance User Interface (2002) http://carbon.uab.es/mrui.Google Scholar
Malenfant, P, Tremblay, A, Doucet, E, Imbeault, P, Simoneau, JA & Joanisse, DR (2001) Elevated intramyocellular lipid concentration in obese subjects is not reduced after diet and exercise training. American Journal of Physiology 280, E632–E639.Google Scholar
Man, ZW, Hirashima, T, Mori, S & Kawano, K (2002) Decrease in triglyceride accumulation in tissues by restricted diet and improvement of diabetes in Otsuka Long–Evans Tokushima fatty rats, a non-insulin-dependent diabetes model. Metabolism 49, 108–114.CrossRefGoogle Scholar
Matsuda, M & Defronzo, R (1999) Insulin sensitivity indices obtained from oral glucose tolerance testing comparison with the euglycemic insulin clamp. Diabetes Care 22, 1462–1470.CrossRefGoogle ScholarPubMed
Mingrone, G, Bertuzzi, A, Capristo, E, Greco, A, Manco, M, Pietrobelli, A, Salinari, S & Heymsfield, SB (2001) Unreliable use of standard muscle hydration value in obesity. American Journal of Physiology 280, E365–E371.Google ScholarPubMed
Nelson, M, Atkinson, M & Meyer, J (1997) A Photographic Atlas of Food Portion Sizes. London: Ministry of Agriculture, Fisheries and Food.Google Scholar
Oakes, ND, Cooney, GJ, Camilleri, S, Chisholm, DJ & Kraegen, EW (1997) Mechanisms of liver and muscle insulin resistance induced by chronic high-fat feeding. Diabetes 46, 1768–1774.CrossRefGoogle ScholarPubMed
Ohneda, M, Inman, LR & Unger, RH (2002) Caloric restriction in obese pre-diabetic rats prevents beta-cell depletion loss of beta-cell GLUT2 and glucose incompetence. Diabetologia 38, 173–179.CrossRefGoogle Scholar
Pan, DA, Lillioja, S, Kriketos, AD, Milner, MR, Baur, LA, Bogardus, C, Jenkins, AB & Storlien, LH (1997) Skeletal muscle triglyceride levels are inversely related to insulin action. Diabetes 46, 983–988.CrossRefGoogle ScholarPubMed
Phillips, DI, Caddy, S, Ilic, V, Fielding, BA, Frayn, KN, Borthwick, AC & Taylor, R (1996) Intramuscular triglyceride and muscle insulin sensitivity: evidence for a relationship in nondiabetic subjects. Metabolism 45, 947–950.CrossRefGoogle ScholarPubMed
Randle, PJ, Hales, CN, Garland, PB & Newsholme, EA (1963) The glucose fatty-acid cycle: Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet i, 785–789.CrossRefGoogle Scholar
Reaven, GM (1994) Syndrome X: 6 years later. Journal of Internal Medicine i Suppl. 736, 13–22.Google Scholar
Reaven, GM (1995) Pathophysiology of insulin resistance in human disease. Physiology Reviews 75, 473–486.CrossRefGoogle ScholarPubMed
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. Journal of Physiology 510 pt 2, 615–622.CrossRefGoogle ScholarPubMed
Roche, HM (1999) Dietary carbohydrate and triacylglycerol metabolism. Proceedings of the Nutrition Society 58, 201–207.CrossRefGoogle ScholarPubMed
Roden, M, Price, TB, Perseghin, G, Petersen, KF, Rothman, DL, Cline, GW & Shulman, GI (1996) Mechanism of free fatty acid-induced insulin resistance in humans. Journal of Clinical Investigation 97, 2859–2865.CrossRefGoogle ScholarPubMed
Salmeron, J, Ascherio, A, Rimm, EB, Colditz, GA, Spiegelman, D, Jenkins, DJ, Stampfer, MJ, Wing, AL & Willett, W (1997 a) Dietary fiber, glycemic load and risk of NIDDM in men. Diabetes Care 20, 545–550.CrossRefGoogle ScholarPubMed
Salmeron, J, Manson, JE, Stampfer, MJ, Colditz, GA, Wing, AL & Willett, WC (1997 b) Dietary fiber, glycemic load and risk of non-insulin-dependent diabetes mellitus in women. Journal of the American Medical Association 277, 472–477.CrossRefGoogle ScholarPubMed
Saris, WH, Asp, NGL, Bjorck, I, Blaak, E, Bornet, F, Brouns, F, Frayn, KN, Furst, P, Riccardi, G, Roberfroid, M & Vogel, M (1998) Functional food science and substrate metabolism. British Journal of Nutrition 80, S47–S75.CrossRefGoogle ScholarPubMed
Schick, F, Eismann, B, Jung, WI, Bongers, H, Bunse, M & Lutz, O (1993) Comparison of localized proton NMR signals of skeletal muscle and fat tissue in vivo: two lipid compartments in muscle tissue. Magnetic Resonance in Medicine 29, 158–167.CrossRefGoogle ScholarPubMed
Schofield, WN, Schofield, C & James, WPT (1985) Basal metabolic rate–review and prediction. Human Nutrition: Clinical Nutrition 39 Suppl., 1–96.Google Scholar
Sreenan, S, Keck, S, Fuller, T, Cockburn, B & Burant, F (1999) Effects of troglitazone on substrate storage and utilization in insulin-resistant rats. American Journal of Physiology 276, E1119–E1129.Google ScholarPubMed
Stears, AJ & Byrne, CD (2001) Adipocyte metabolism and the metabolic syndrome. Diabetes Obesity and Metabolism 3, 129–142.CrossRefGoogle ScholarPubMed
Storlien, LH, Jenkins, AB, Chisholm, DJ, Pascoe, WS, Khouri, S & Kraegen, EW (1991) Influence of dietary fat composition on development of insulin resistance in rats. Relationship to muscle triglyceride and n-3 fatty acids in muscle phospholipids. Diabetes 40, 280–289.CrossRefGoogle Scholar
Thomas, EL, Frost, G, Harrington, T & Bell, JD (2001) Validation of "in body" bioelectrical impedance by whole body MRI. Proceedings of the Nutrition Society 60, 96A.Google Scholar
Thorburn, A, Muir, J & Proietto, J (1993) Carbohydrate fermentation decreases hepatic glucose output in healthy subjects. Metabolism 42, 780–785.CrossRefGoogle ScholarPubMed
Torjesen, PA, Birkeland, KI, Anderssen, SA, Hjermann, I, Holme, I & Urdal, P (1997) Lifestyle changes may reverse development of the insulin resistance syndrome. The Oslo Diet and Exercise Study: a randomized trial. Diabetes Care 20, 26–31.CrossRefGoogle ScholarPubMed
Tremblay, A (1995) Nutritional determinants of the insulin resistance syndrome. International Journal of Obesity 19 Suppl., S60–S68.Google ScholarPubMed
Van Dam, RM, Visscher, AW, Feskens, EJ, Verhoef, P & Kromhout, D (2000) Dietary glycaemic index in relation to metabolic risk factors and incidence of coronary heart disease: the Zirtphen Elderly Study. European Journal of Clinical Nutrition 54, 726–731.CrossRefGoogle ScholarPubMed
van den Boogaart, A, van Heke, P, van Huffel, S, Graveron-Demilly, D, van Ormondt, D & de Beer, R (1996) MRUI: a graphical user interface for accurate routine MRS data analysis. In Proceedings of the ESMRMB, 13th Annual Meeting of the ESMRMB, pp. 318.Google Scholar
Voshol, PJ, Jong, MC, Dahlmans, VE, Kratky, D, Levak-Frank, S, Zechner, R, Romijn, JA & Havekes, LM (2001) In muscle-specific lipoprotein lipase-overexpressing mice muscle triglyceride content is increased without inhibition of insulin-stimulated whole-body and muscle-specific glucose uptake. Diabetes 50, 2585–2590.CrossRefGoogle ScholarPubMed
Wolever, T, Jenkins, DJ, Vuksan, V, Jenkins, AL, Buckley, G, Wong, GS & Josse, RG (1992) Beneficial effect of a low glycaemic index diet in type 2 diabetes. (Abstr). Diabetic Medicine 9, 451–458.CrossRefGoogle Scholar
Wolever, TM, Bentum, WA & Jenkins, DJ (1995) Physiological modulation of plasma free fatty acid concentrations by diet. Metabolic implications in nondiabetic subjects. Diabetes Care 18, 962–970.CrossRefGoogle ScholarPubMed
Wolever, TM & Jenkins, DJ (1986) The use of the glycemic index in predicting the blood glucose response to mixed meals. American Journal of Clinical Nutrition 43, 167–172.CrossRefGoogle ScholarPubMed