Horm Metab Res 2008; 40(7): 459-466
DOI: 10.1055/s-2008-1065318
Animals, Clinical

© Georg Thieme Verlag KG Stuttgart · New York

Induction and Reversibility of Insulin Resistance in Rats Exposed to Exogenous D-Fructose

J. Cancelas 1 , P. G. Prieto 1 , M. García-Arévalo 1 , V. Sancho 1 , M. L. Villanueva-Peñacarrillo 1 , W. J. Malaisse 2 , I. Valverde 1
  • 1Department of Metabolism, Nutrition and Hormones, Fundacíón Jiménez Díaz, Madrid, Spain
  • 2Laboratory of Experimental Hormonology, Brussels Free University, Brussels, Belgium
Further Information

Publication History

received 23.04.2007

accepted 06.11.2007

Publication Date:
07 April 2008 (online)

Abstract

Long-term exposure of normal rats to a fructose-enriched diet or drinking water is currently used as an animal model for experimental insulin resistance. The present study deals with a comparison between rats given access to either a fructose-enriched diet or fructose-enriched drinking water. In both situations, a decrease in food intake and body weight gain, and the induction of insulin resistance with intolerance to D-glucose despite increased secretory response to the aldohexose of insulin-producing cells were documented. Moreover, the rats exposed to exogenous D-fructose displayed a lesser sensitivity to overnight fasting than control animals, in terms of the alteration of glucose homeostasis and reduction of the ratio between plasma insulin and D-glucose concentration. It is also shown that the fructose-induced insulin resistance, as assessed in a hyperinsulinemic-euglycemic clamp, represents a phenomenon reversed within 15–30 days after removal of the keto-hexose from the drinking water.

References

  • 1 Bloomgarden ZT. Insulin resistance, dyslipidemia, and cardiovascular disease.  Diabetes Care. 2007;  30 2164-2170
  • 2 Prieto PG, Cancelas J, Villanueva-Peñacarrillo ML, Valverde I, Malaisse WJ. Short-term and long-term effects of guar on postprandial plasma glucose, insulin and glucagon-like peptide 1 concentration in healthy rats.  Horm Metab Res. 2006;  38 397-404
  • 3 Prieto PG, Cancelas J, Moreno P, Villanueva-Penacarrillo ML, Malaisse WJ, Valverde I. Effects of diet supplementation with olive oil and guar upon fructose-induced insulin resistance in normal rats.  Endocrine. 2007;  31 294-299
  • 4 Prieto PG, Cancelas J, Villanueva-Peñacarrillo ML, Valverde I, Malaisse WJ. Plasma D-glucose, D-fructose and insulin responses after oral administration of D-glucose, D-fructose and sucrose to normal rats.  J Am Coll Nutr. 2004;  23 414-419
  • 5 Kamata K, Yamashita K. Insulin resistance and impaired endothelium-dependent renal vasodilatation in fructose-fed hypertensive rats.  Res Commun Mol Pathol Pharmacol. 1999;  103 195-210
  • 6 Catena C, Giacchetti G, Novello M, Colussi G, Cavarape A, Sechi LA. Cellular mechanisms of insulin resistance in rats with fructose-induced hypertension.  Am J Hypertens. 2003;  16 973-978
  • 7 Nandhini AT, Thirunavukkarasu V, Anuradha CV. Taurine modifies insulin signaling enzymes in the fructose-fed insulin resistant rats.  Diabetes Metab. 2005;  31 337-344
  • 8 Chang JC, Wu MC, Liu IM, Cheng JT. Increase of insulin sensitivity by stevioside in fructose-rich chow-fed rats.  Horm Metab Res. 2005;  37 610-616
  • 9 Lee WK, Kao ST, Liu IM, Cheng JT. Ginsenoside Rh2 is one of the active principles of Panax ginseng root to improve insulin sensitivity in fructose-rich chow-fed rats.  Horm Metab Res. 2007;  39 347-354
  • 10 Escriva F, Agote M, Rubio E, Molero JC, Pascual-Leone AM, Andres A, Satrustegui J, Carrascosa JM. In vivo insulin-dependent glucose uptake of specific tissues is decreased during aging of mature Wistar rats.  Endocrinology. 1997;  138 49-54
  • 11 Bergmeyer HU, Berndt E. Glucose determination with glucose oxidase and peroxidase. In: Bergmeyer HU (ed). Methods of Enzymatic Analysis. New York: Academic Press 1974: 1205-1215
  • 12 Valverde I, Barreto M, Malaisse WJ. Stimulation by D-glucose of protein biosynthesis in tumoral insulin-producing cells (RINm5F line).  Endocrinology. 1988;  122 1443-1448
  • 13 Cancelas J, Sancho V, Villanueva-Penacarrillo ML, Courtois P, Scott FW, Valverde I, Malaisse WJ. GLP-1 content of the intestinal tract in adult rats injected with streptozotocin either during the neonatal period or seven days before sacrifice.  Endocrine. 2002;  19 279-286
  • 14 Jackson RL, Shuey EW, Grinnan EL, Ellis RM. Preparation and partial characterization of crystalline human insulin.  Diabetes. 1969;  18 206-211
  • 15 Viñambres C, Villanueva-Peñacarrillo ML, Valverde I, Malaisse WJ. Failure of D-fructose to stimulate protein biosynthesis in pancreatic islets.  Biochem Mol Biol Int. 1997;  41 571-574

Correspondence

I. ValverdeMD, PhD 

Metabolismo Nutrición y Hormonas

Fundación Jiménez Díaz

Avda. Reyes Católicos 2

28040 Madrid

Spain

Phone: +34/915/50 48 99

Fax: +34/915/44 02 47

Email: ivalverde@fjd.es