Subscribe to RSS
Download PDF
DOI: 10.1055/s-2001-15412
© Georg Thieme Verlag Stuttgart · New York
Effects of Troglitazone and Voluntary Running on Insulin Resistance Induced High Fat Diet in the Rat
Publication History
Publication Date:
31 December 2001 (online)
It is well known that troglitazone and voluntary running have the capacity to improve insulin resistance. The purpose of this study was to evaluate the combination effect of troglitazone and voluntary running on insulin action. Female rats aged 7 weeks were divided into high-fat diet (HF), high-fat diet + troglitazone (0.3 % in diet; Tg), high-fat diet + voluntary running (for 3 wks; Tr), high-fat diet + troglitazone + voluntary running (Tg-Tr), and control (C) groups. A sequential euglycemic clamp experiment with two different insulin infusion rates of 3.0 (L-clamp) and 30.0 mU/kg BW/min (H-clamp) was performed on these rats after an overnight fast. Blood glucose concentrations were kept at fasting levels by periodic adjustment of the intravenous glucose infusion rate during the clamp experiment. Glucose infusion rates (GIRs) calculated from 60 to 90, 150 to 180 min were regarded as an index of whole body insulin action. After the clamp experiment, we determined the amount of glycogen content in the gastrocnemius muscle. Fat feeding markedly reduced GIRs in both L- and H- clamp experiments compared with C. Troglitazone treatment did not improve high-fat induced insulin resistance. In both L- and H-clamp experiments, GIRs were increased by voluntary running compared with HF, and reached the same levels as in C. GIRs of Tg-Tr were not greater than those of Tr. Glycogen content in gastrocnemius muscle showed the same trend as the results for GIRs. Therefore, the combination effect of troglitazone and voluntary running on insulin action was not found, but the effect of voluntary running was shown in fat-induced insulin resistance.
Key words:
Thiazolidinediones - Euglycemic Clamp - Glycogen
References
- 1 Kahn C R. Causes of insulin resistance. Nature. 1995; 373 384-385
- 2 Fujita T, Sugiyama Y, Taketomi S, Sohda T, Kawamatsu Y, Iwatsuka H, Suzuoki Z. Reduction of insulin resistance in obese and/or diabetic animals by 5-[4-(l-methylcyclohexylmethoxy)benzyl]-thiazolidine-2,4-dione (ADD-3878, U-63,287, ciglitazone), a new antidiabetic agent. Diabetes. 1983; 32 (9) 804-810
- 3 Fujiwara T, Yoshioka S, Yoshioka T, Ushiyama I, Horikoshi H. Characterization of new oral antidiabetic agent CS-045. Studies in KK and ob/ob mice and Zucker fatty rats. Diabetes. 1988; 37 (11) 1549-1558
- 4 Lee M K, Miles P D, Khoursheed M, Gao K M, Moossa A R, Olefsky J M. Metabolic effects of troglitazone on fructose-induced insulin resistance in the rat. Diabetes. 1994; 43 (12) 1435-1439
- 5 Oakes N D, Kennedy C J, Jenkins A B, Laybutt D R, Chisholm D J, Kraegen E W. A new antidiabetic agent, BRL 49 653, reduces lipid availability and improves insulin action and glucoregulation in the rat. Diabetes. 1994; 43 (10) 1203-1210
- 6 Kellerer M, Kroder G, Tippmer S, Berti L, Kiehn R, Mosthaf L, Haring H. Troglitazone prevents glucose-induced insulin resistance of insulin receptor in rat-1 fibroblasts. Diabetes. 1994; 43 (3) 447-453
- 7 Iwamoto Y, Kuzuya T, Matsuda A, Awata T, Kumakura S, Inooka G, and Shiraishi I. Effect of new antidiabetic agent CS-045 on glucose tolerance and insulin secretion in patients with NIDDM. Diabetes Care. 1991; 14 1083-1086
- 8 Kumar S, Boulton A J, Beck-Nielsen H, Berthezene F, Muggeo M, Persson B, Spinas G A, Donoghue S, Lettis S, Stewart-Long P. Troglitazone, an insulin action enhancer, improves metabolic control in NIDDM patients. Diabetologia. 1996; 39 (6) 701-709
- 9 Lehmann J M, Moore L B, Smith-Oliver T A, Wilkison W O, Willson T M, Kliewer S A. An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma). J Biol Chem. 1995; 270 (22) 12 953-12 956
- 10 Okuno A, Tamemoto H, Tobe K, Ueki K, Mori Y, Iwamoto K, Umesono K, Akanuma Y, Fujiwara T, HorikoshH, Yazaki Y, Kadowaki T. Troglitazone increases the number of small adipocytes without the change of white adipose tissue mass in obese Zucker rats. J Clin Invest. 1998; 101 1354-1361
- 11 Hokama J Y, Streeper R S, Henriksen E J. Voluntary exercise training enhances glucose transport in muscle stimulated by insulin-like growth factor I. J Appl Physiol. 1997; 82 (2) 508-512
- 12 Edelman S V, Laakso M, Wallace P, Brechtel G, Olefsky J M, Baron A D. Kinetics of insulin-mediated and non-insulin-mediated glucose uptake in humans. Diabetes. 1990; 39 (8) 955-964
- 13 Miller W J, Sherman W M, Ivy J L. Effect of strength training on glucose tolerance and post-glucose insulin response. Med Sci Sports Exerc. 1984; 16 (6) 539-543
- 14 Torgan C E, Brozinick J T, Banks E A, Cortez M Y, Wilcox R E, Ivy J L. Exercise training and clenbuterol reduce insulin resistance of obese Zucker rats. Am J Physiol. 1993; 264 (3 Ptl) ¥373-¥379
- 15 Ploug T, Stallknecht B M, Pedersen O, Kahn B B, Ohkuwa T, Vinten J, Galbo H. Effect of endurance training on glucose transport capacity and glucose transporter expression in rat skeletal muscle. Am J Physiol. 1990; 259 (6 Pt 1) E778-E786
- 16 Banks E A, Brozinick J T, Yaspelkis BB I II, Kang H Y, Ivy J L. Muscle glucose transport, GLUT-4 content, and degree of exercise training in obese Zucker rats. Am J Physiol. 1992; 263 (5 Pt 1) E1010-E1015
- 17 Storlien L H, Baur L A, Kriketos A D, Pan D A, Cooney G J, Jenkins A B, Calvert G D, Campbell L V. Dietary fats and insulin action. Diabetologia. 1996; 39 (6) 621-631
- 18 DeFronzo R A, Tobin J D, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol. 1979; 237 (3) E214-E223
- 19 Johnson H D, Ward M W, Kibler H H. Heat and aging effects on thyroid function of male rats. J Appl Physiol. 1966; 21 689-694
- 20 Davidson M B, Garvey D. Studies on mechanisms of hepatic insulin resistance in cafeteria-fed rats. Am J Physiol. 1993; 264 (I Pt 1) E18-E23
- 21 Storlien L H, Pan D A, Kriketos A D, Baur L A. High fat diet-induced insulin resistance. Ann NY Acad Sci. 1993; 683 82-90
- 22 Vrana A, Kazdova L, Dobesova Z, Kunes J, Kren V, Bila V, Stolba P, Klimes I. Triglyceridemia, glucoregulation, and blood pressure in various rat strains. Effects of dietary carbohydrates. Ann NY Acad Sei. 1993; 683 57-68
- 23 Randle P J, Garland P B, Haies C N, Newsholme E A. The glucose fatty-acid cycle: its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet. 1963; 1 785-789
- 24 Boden G. Role of fatty acids in the pathogenesis of insulin resistance and NIDDM. Diabetes. 1997; 46 3-10
- 25 Hotamisligil G S, Murray D L, Choy L N, Spiegelman B M. Tumor necrosis factor alpha inhibits signaling from the insulin receptor. Proceedings of the National Academy of Sciences of the United States of America. 1994; 91 (11) 4854-4858
- 26 Hotamisligil G S, Budavari A, Murray D, Spiegelman B M. Reduced tyrosine kinase activity of the insulin receptor in obesity-diabetes. Central role of tumor necrosis factor-alpha. J Clin Invest. 1994; 94 (4) 1543-1549
- 27 Segal K R, Landt M, Klein S. Relationship between insulin sensitivity and plasma leptin concentration in lean and obese men. Diabetes. 1996; 45 (7) 988-991
- 28 Müller G, Ertl J, Gerl M, Preibisch G. Leptin impairs metabolic actions of insulin in isolated rat adipocytes. J Biol Chem. 1997; 272 (16) 10 585-10 593
- 29 Hofmann C A, Colca J R. New oral thiazolidinedione antidiabetic agents act as insulin sensitizers. Diabetes Care. 1992; 15 (8) 1075-1078
- 30 Suter S L, Nolan J J, Wallace P, Gumbiner B, Olefsky J M. Metabolic effects of new oral hypoglycemic agent CS-045 in NIDDM subjects. Diabetes Care. 1992; 15 (2) 193-203
- 31 Fujiwara T, Okuno A, Yoshioka S, Horikoshi H. Suppression of hepatic gluconeogenesis in long-term troglitazone treated diabetic KK and C57BL/KsJ-db/db mice. Metabolism. 1995; 44 (4) 486-490
- 32 Tontonoz P, Hu E, Spiegelman B M. Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor. Cell. 1994; 79 (7) 1147-1156
- 33 Braissant O, Foufelle F, Scotto C, Dauca M, Wahli W. Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat. Endocrinology. 1996; 137 (1) 354-366
- 34 Mott D M, Lillioja S, Bogardus C. Overnutrition induced decrease in insulin action for glucose storage: in vivo and in vitro in man. Metabolism. 1986; 35 (2) 160-165
- 35 Lawrence JC J r, Colvin J, Cartee G D, Holloszy J O. Effects of aging and exercise on insulin action in rat adipocytes are correlated with changes in fat cell volume. J Gerontol. 1989; 44 (4) B88-B92
- 36 Laakso M, Edelman S V, Brechtel G, Baron A D. Impaired insulin-mediated skeletal muscle blood flow in patients with NIDDM. Diabetes. 1992; 41 (9) 1076-1083
- 37 Phillips S M, Han X X, Green H J, Bonen A. Increments in skeletal muscle GLUT-1 and GLUT-4 after endurance training in humans. Am J Physiol. 1996; 270 (3 Pt 1) E456-E462
- 38 Ivy J L, Frishberg B A, Farrell S W, Miller W J, Sherman W M. Effects of elevated and exercise-reduced muscle glycogen levels on insulin sensivity. J Appl Physiol. 1985; 59 154-159
- 39 Henriksen E J, Bourey R E, Rodnick K J, Koranyi L, Permutt M A, Holloszy J O. Glucose transporter protein content and glucose transport capacity in rat skeletal muscles. Am J Physiol (Endocrinol Metab 22). 1990; 259 E593-E598
- 40 Lee M K, Miles P D, Khoursheed M, Gao K M, Moossa A R, Olefsky J M. Metabolie effects of troglitazone on fructose-induced insulin resistance in the rat. Diabetes. 1994; 43 (12) 1435-1439
- 41 Miles P D, Romeo O M, Higo K, Cohen A, Rafaat K, Olefsky J M. TNF-alpha-induced insulin resistance in vivo and its prevention by troglitazone. Diabetes. 1997; 46 (I 1) 1678-1683
- 42 Khoursheed M, Miles P D, Gao K M, Lee M K, Moossa A R, Olefsky J M. Metabolic effects of troglitazone on fat-induced insulin resistance in the rat. Metabolism. 1995; 44 (11) 1489-1494
Y. Sato
Research Center of Health, Physical Fitness and Sports
Nagoya University, Furo-cho
Chikusa-ku, Nagoya 464-8601
Japan
Phone: Phone:+ 81 (52) 789-3962
Fax: Fax:+ 81 (52) 789-3957
Email: E-mail:ysato@med.nagoya-u.ac.jp