Effects of high-sucrose feeding on insulin resistance and hemodynamic responses to insulin in spontaneously hypertensive rats

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 290; no. 6; pp. H2571 - H2581
• Main Authors: Melancon, Sebastien, Bachelard, Helene, Badeau, Mylene, Bourgoin, Frederic, Pitre, Maryse, Lariviere, Richard, Nadeau, Andre
• Format: Journal Article
• Language: English
• Published: United States 01.06.2006
• Subjects: Animals; Blotting, Western; Deoxyglucose - metabolism; Deoxyglucose - pharmacology; Dose-Response Relationship, Drug; Endothelin-1 - pharmacology; Fructose - pharmacology; Glucose Clamp Technique; Hemodynamics - drug effects; Hyperinsulinism - physiopathology; Hypertension - genetics; Hypertension - physiopathology; Hypoglycemic Agents - pharmacology; Insulin - pharmacology; Insulin Resistance - genetics; Male; Muscle, Skeletal - drug effects; Muscle, Skeletal - enzymology; Nitric Oxide Synthase Type III - biosynthesis; Nitric Oxide Synthase Type III - genetics; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Regional Blood Flow - drug effects; Sucrose - pharmacology
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.01002.2005

1 Department of Medicine and Lipid Research Unit, 2 Research Center of L'Hôtel Dieu de Québec, and 3 Diabetes Research Unit, Centre Hospitalier Universitaire de Québec, Laval University, Sainte-Foy, Quebec, Canada Submitted 19 September 2005 ; accepted in final form 18 January 2006 This study was designed to investigate the effects of a sucrose diet on vascular and metabolic actions of insulin in spontaneously hypertensive rats (SHR). Male SHR were randomized to receive a sucrose or regular chow diet for 4 wk. Age-matched, chow-fed Wistar-Kyoto (WKY) rats were used as normotensive control. In a first series of experiments, the three groups of rats had pulsed Doppler flow probes and intravascular catheters implanted to determine blood pressure, heart rate, and blood flows. Insulin sensitivity was assessed during a euglycemic hyperinsulinemic clamp performed in conscious rats. In a second series of experiments, new groups of rats were used to examine glucose transport activity in isolated muscles and to determine endothelial nitric oxide synthase (eNOS) protein expression in muscles and endothelin content in vascular tissues. Sucrose feeding was shown to markedly enhance the pressor response to insulin and its hindquarter vasoconstrictor effect when compared with chow-fed SHR. A reduction in eNOS protein content in muscle, but no change in vascular endothelin-1 protein, was noted in sucrose-fed SHR when compared with WKY rats, but these changes were not different from those noted in chow-fed SHR. Similar reductions in insulin-stimulated glucose transport were observed in soleus muscles from both groups of SHR when compared with WKY rats. In extensor digitorum longus muscles, a significant reduction in insulin-stimulated glucose transport was only seen in sucrose-fed rats when compared with the other two groups. Environmental factors, that is, high intake of simple sugars, could possibly potentiate the genetic predisposition in SHR to endothelial dysfunction and insulin resistance. hypertension; insulin vascular effects; nitric oxide synthase Address for reprint requests and other correspondence: H. Bachelard, Lipid Research Unit, Centre de Recherche du CHUL, CHUQ, 2705 Blvd. Laurier, Ste-Foy, Quebec, Canada, G1V 4G2 (e-mail: helene.bachelard{at}crchul.ulaval.ca )