Horm Metab Res 2002; 34(7): 360-366
DOI: 10.1055/s-2002-33467
Original Basic
© Georg Thieme Verlag Stuttgart · New York

Regulation of Glucose Transport and Transporter 4 (GLUT-4) in Muscle and Adipocytes of Sucrose-Fed Rats: Effects of N-3 Poly- and Monounsaturated Fatty Acids

E.  Peyron-Caso 1 , S.  Fluteau-Nadler 1 , M.  Kabir 1 , M.  Guerre-Millo 2 , A.  Quignard-Boulangé 2 , G.  Slama 1 , S.  W.  Rizkalla 1
  • 1Department of Diabetes-INSERM U341, Hôtel-Dieu Hospital, Paris, France
  • 2 INSERM U465, Paris, France
Further Information

Publication History

Received: 11 October 2001

Accepted after revision: 19 March 2002

Publication Date:
21 August 2002 (online)

Abstract

The goal of this study was to compare the short-term effects of dietary n-3 polyunsaturated (fish oil) and monounsaturated (olive oil) fatty acids on glucose transport, plasma glucose and lipid controls in a dietary insulin resistance model using sucrose-fed rats. The underlying cellular and molecular mechanisms were also determined in the muscle and adipose tissue. Male Sprague-Dawley rats (5 weeks old) were randomized for diets containing 57.5 % (w/w) sucrose and 14 % lipids as either fish oil (SF), olive oil (SO) or a mixture of standard oils (SC) for 3 weeks. A fourth control group (C) was fed a diet containing 57.5 % starch and 14 % standard oils. After three weeks on the diet, body weight was comparable in the four groups. The sucrose-fed rats were hyperglycemic and hyperinsulinemic in response to glucose load. The presence of fish oil in the sucrose diet prevented sucrose-induced hyperinsulinemia and hypertriglyceridemia, but had no effect on plasma glucose levels. Insulin-stimulated glucose transport in adipocytes increased after feeding with fish oil (p < 0.005). These modifications were associated with increased Glut-4 protein (p < 0.05) and mRNA levels in adipocytes. In the muscle, no effect was found on Glut-4 protein levels. Olive oil, however, could not bring about any improvement in plasma insulin, plasma lipids or Glut-4 protein levels. We therefore conclude that the presence of fish oil, in contrast to olive oil, prevents insulin resistance and hypertriglyceridemia in rats on a sucrose diet, and restores Glut-4 protein quantity in adipocytes but not in muscle at basal levels. Dietary regulation of Glut-4 proteins appears to be tissue specific and might depend on insulin stimulation and/or duration of dietary interventions.

References

  • 1 Bang H O, Dyeberg J, Nielsen A B. Plasma lipid and lipoprotein pattern in greenland west coast Eskimos.  Lancet. 1971;  1 143-1145
  • 2 Keys A, Menotti A, Aravanis C. The seven countries study: 2289 deaths in 15 years.  Prev Med. 1984;  13 141-154
  • 3 Kasime E, Stern B, Khilnani S, Lin P M, Baciorowski S, Jen K L. Effects of omega-3 fish oils on lipid metabolism, glycemic control, and blood pressure in type 2 diabetic patients.  J Clin Endoc Met. 1988;  67 1-5
  • 4 Glauber H, Wallace P, Griver K, Brechtel G. Adverse metabolic effect of omega-3 fatty acids in non insulin dependent diabetes mellitus.  Ann Intern Med. 1988;  108 663-668
  • 5 Friday K, Childs M, Tsunehara C, Fugimoto W, Bierman E. Elevated plasma glucose and lowered triglyceride levels from omega-3 fatty acid supplementation in type 2 diabetes.  Diabetes Care. 1989;  12, 4 276-281
  • 6 Garg A. Treatment of diabetic dyslipidemia.  Am J Cardiol. 1998;  81 47B-51B
  • 7 Campbell L V, Marmot P E, Dyer J A, Borckman M, Storlien L H. The high monounsaturated fat diet as a practical alternative for NIDDM.  Diabetes care. 1994;  17 (3) 177-182
  • 8 Garg A, Bantle J P, Henry R, Coulstom A M, Griver K A, Raatz S K, Brinkley L, Chen I, Grundy S M, Huet B A, Reaven G M. Effects of varying carbohydrate content of diet in patients with non-insulin-dependant diabetes mellitus.  JAMA. 1994;  271 1421-1428
  • 9 Storlien L H, Kraegen E W, Chisholm D J, Ford G L, Bruce D G, Pascoe W S. Fish oil prevents insulin resistance induced by high fat feeding.  Science. 1987;  237 885-888
  • 10 Luo J, Rizkalla S W, Boillot J, Alamowitch C, Chaib H, Bruzzo F, Desplanque N, Dalix A M, Durand G, Slama G. Dietary (n-3) polyunsaturated fatty acids improve adipocyte insulin action and glucose metabolism in insulin-resistant rats: relation to membrane fatty acids.  J Nutr. 1996;  126 (8) 1951-1958
  • 11 Kim J, Nolte L, Hansen P, Han D, Freguson K, Thompson P, Holloszy J. High-fat diet-induced muscle insulin resistance: relationship to visceral fat mass.  Am J Physiol. 2000;  279 R2057-R2065
  • 12 Rodbell M. Effects of hormones on glucose metabolism and lipolysis.  J Biol Chem. 1964;  239 375-380
  • 13 Lavau M, Susini C, Knittle J, Blanchet-Hirst S, Greenwood M R. A reliable photomicrographic method for determining fat cell size and number: application for dietary obesity.  Proc Soc Exp Biol Med. 1977;  156 251-256
  • 14 Goldrick R B. Morphological changes in adipocyte timing of fat deposition and mobilization.  Am J Physiol. 1967;  212 777-782
  • 15 Dole V P, Meinertz H. Microdetermination of long-chain fatty acids in plasma and tissues.  J Biol Chem. 1960;  235 2595-2599
  • 16 Guerre-Millo M, Lavau M, Horne J S, Wardzala L J. Proposed mechanism for increased insulin-mediated glucose transport in adipose cells from young, obese Zucker rats. Large intracellular pool of glucose transporters.  J Biol Chem. 1985;  260 2197-2201
  • 17 Joost H G, Weber T M, Cushman S W. Qualitative and quantitative comparison of glucose transport activity and glucose transporter concentration in plasma membranes from basal and insulin-stimulated rat adipose cells.  Biochem J. 1988;  249 155-161
  • 18 Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidium thiocyanate-phenol-chloroform extraction.  Ann Biochem. 1987;  162 156-159
  • 19 Janke J, Engeli S, Gorzelniak K, Sharma A M. Extraction of total RNA from adipocytes.  Horm Metab Res. 2001;  33 213-215
  • 20 Charron J M. A glucose transport protein expressed predominately in insulin-responsive tissues.  PNAS USA. 1989;  86 2535-2539
  • 21 Gorzelniak K, Janke J, Engeli S, Sharma A M. Validation of endogenous controls for gene expression studies in human adipocytes and preadipocytes.  Horm Metab Res. 2001;  33 625-627
  • 22 Breil V, Rouault C, Rizkalla S W, Broca C, Taouis M, Petit P, Reach G. 4-Hydroxyisoleucine improves insulin sensitivity in insulin resistant rats. Effect of 4-hydroxyisoleucine on insulin sensitivity. Diabetes (submitted in 2002)
  • 23 Breil V, Rouault C, Rizkalla S W, Broca C, Taouis M, Petit P, Reach G. Effect of 4-hydroxyisoleucine on insulin sensitivity in insulin resistant rats.  Diabetologia. 2001;  44 Suppl. 1 A79
  • 24 Storlien L H, Kraegen E W, Jenkins A B, Chisholm D J. Effects of sucrose vs. starch diets on in vivo insulin action, thermogenesis, and obesity in rats.  Am J Clin Nutr. 1988;  47 420-427
  • 25 D’Alessandro M E, Chicco A, Karabatas L, Lombardo Y B. Role of skeletal muscle on impaired insulin sensitivity in rats fed a sucrose-rich diet: Effect of moderate levels of dietary fish oil.  J Nutr Biochem. 2000;  11 273-280
  • 26 Kim J, Notle L, Hansen P, Han D, Kawanaka K, Holloszy J. Insulin resistance of muscle glucose transport in male and female rats fed high-sucrose diet.  Am J Physiol. 1999;  276 R665-R672
  • 27 Vrana A, Kazdova L. Effects of dietary sucrose and fructose on carbohydrate and lipid metabolism.  Animal studies Prog Biochem Pharmacol. 1986;  21 59-73
  • 28 Podolin D A, Gayles E C, Wei Y, Thresher J S, Pagliassotti M J. Menhaden oil prevents but not reverse sucrose-induced insulin resistance in rats.  Am J Physiol. 1998;  274 R840-R848
  • 29 Riccardi G, Rivellese A A. Dietary treatment of the metabolic syndrome - the optimal diet.  Br J Nutr. 2000;  83, 1 S143-S148
  • 30 Zisman A, Peroni O D, Abel E D, Michael M D, Mauvais-Jarvis F, Lowell-Wojtaszewski J F, Hirshman M F, Virkamaki A, Goodyear L J, Khan C R, Khan B B. Targeted disruption of the glucose transporter 4 selectively in muscle causes insulin resistance and glucose intolerance.  Nat Med. 2000;  6 924-928
  • 31 Giron M, Salto R, Hortelano P, Periago J, Vargas A, Suarez M. Increased diaphragm expression of GLUT4 in control and streptozotocin-diabetic rats by fish oil-supplemented diets.  Lipids. 1999;  34 801-807
  • 32 Klimes I, Sebokova E, Minchenko A, Maassen T, Moss R, Mitkova A, Wiersma M, Bohov P. Glut-4 gene expression and Glut-4 protein levels in muscle of high sucrose-fed rats: effects of dietary fish oil.  J Nutr Biochem. 1994;  5 389-396
  • 33 Sebokova E, Klimes I, Moss R, Mitkova A, Wiersma M, Bohov P. Decreased glucose transporter protein (GLUT4) in skeletal muscle of hypertriglyceridaemic insulin-resistant rat.  Physiol Res. 1995;  44 87-92
  • 34 Mori Y, Murakawa Y, Katoh S, Hata S, Yokoyama J, Tajima N, Ikeda Y, Nobukata H, Ishikawa T, Shibutani Y. Influence of highly purified eicosapentaenoic acid ethyl ester on insulin resistance in the Otsuka Long-Evans Tokushima Fatty rat, a model of spontaneous non-insulin-dependent diabetes mellitus.  Metabolism. 1997;  46 1458-1464
  • 35 Kainulainen H, Komulainen J, Joost H G, Vihko V. Dissociation of the effects of training on oxidative metabolism, glucose utilisation and GLUT-4 levels in skeletal muscle of streptozotocin-diabetic rats.  European Journal of Physiology. 1994;  427 444-449
  • 36 Kern M, Loomis T A, Tapscott E B, Dohm G L. Increased muscle glucose uptake in response to chronic glyburide treatment is not related to changes in glucose transporter (GLUT-4) protein.  Int J Biochem. 1993;  25 1257-1261
  • 37 Kahn B B, Pederson O. Suppression of GLUT-4 expression in skeletal muscle of rats that are obese from high fat feeding but not from high carbohydrate feeding or genetic obesity.  Endocrinology. 1993;  132 13-22
  • 38 Ezaki O, Tsuji E, Momomura K, Kasuga M, Itakura H. Effects of fish and safflower oil feeding on subcellular glucose transporter distributions in rat adipocytes.  Am J Physiol. 1992;  263 E94-E101

Dr. S. W. Rizkalla

Service de diabétologie · INSERM U341

Hôpital Hôtel-Dieu

1 place du parvis Notre-Dame · 75 181 Paris, Cedex 04 · France ·

Phone: + 33 (1) 42 34 83 95

Email: salwa.rizkalla@htd.ap-hop-paris.fr

    >