Malonyl coenzyme A and adiposity in the Dahl salt-sensitive rat: effects of pioglitazone

Metabolism: Clinical and Experimental
T G KurowskiNeil B Ruderman

Abstract

These studies were designed to assess the effects of pioglitazone, a new oral antidiabetic agent that acts by improving insulin sensitivity, on blood pressure, plasma and tissue lipids, and insulin resistance in the Dahl salt-sensitive (Dahl-S) rat. Reaven et al had reported that male Dahl-S rats are moderately hyperinsulinemic and insulin-resistant. This was of particular interest since these rats are not obese but are hypertriglyceridemic, and on a high-salt diet they become hypertensive. In the current study, male Sprague-Dawley control and Dahl-S rats were compared when fed standard chow of high-fat, high-sucrose (HFHS) diets with or without pioglitazone (20 mg/kg body weight/d) for 3 weeks. On the standard chow diet, Dahl-S rats were hypertriglyceridemic and had high tissue levels of malonyl coenzyme A ([CoA] Dahl-S 5.0 v control 3.3 nmol/g in muscle, and Dahl-S 15.6 v control 10.7 nmol/g in liver); however, they were not hyperinsulinemic. Pioglitazone therapy decreased both malonyl CoA and plasma triglycerides toward control values, but had no effect on plasma insulin levels. On the HFHS diet, both groups became glucose-intolerant and hyperinsulinemic; however, the hyperinsulinemia was greater and more sustained in Dahl-S...Continue Reading

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Citations

Dec 31, 1997·The American Journal of Physiology·C Schmitz-PeifferT J Biden
Jul 27, 2001·Archives of Physiology and Biochemistry·J UkropecI Klimes
Nov 5, 1997·Annals of the New York Academy of Sciences·N B RudermanT G Kurowski
Apr 23, 1999·Journal of Basic and Clinical Physiology and Pharmacology·N B Ruderman, D Dean
Jan 14, 1999·The American Journal of Physiology·N B RudermanL A Witters
Jan 22, 2004·Biochemical and Biophysical Research Communications·Asish K SahaNeil B Ruderman

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