The antihyperglycemic agent englitazone prevents the defect in glucose transport in rats fed a high-fat diet.

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Title:	The antihyperglycemic agent englitazone prevents the defect in glucose transport in rats fed a high-fat diet.
Author:	Stevenson, R W : McPherson, R K : Persson, L M : Genereux, P E : Swick, A G : Spitzer, J : Herbst, J J : Andrews, K M : Kreutter, D K : Gibbs, E M
Citation:	Diabetes. 1996 Jan; 45(1): 60-6
Abstract:	The effects of englitazone in male Wistar rats fed a high-fat diet (59% of calories as fat) were compared with control rats fed a high-carbohydrate diet (69% of calories as carbohydrate) (5-15 animals per group). Insulin-stimulated (17 nmol/l) 2-deoxy-D-glucose (2-DG) uptake was inhibited 31% in adipocytes isolated from rats on the high-fat diet for 3 weeks, but englitazone (50 mg/kg for the last 7 days) normalized the response. There was a selective decrease in GLUT4 (54 +/- 5% of high-carbohydrate) in epididymal fat from rats on the high-fat diet for 3 weeks, but englitazone treatment did not reverse the defect in GLUT4 (43 +/- 8% of high-carbohydrate) or increase GLUT1 (81 +/- 12% of high-carbohydrate). Englitazone normalized oral glucose (1 g/kg body wt) intolerance and excessive (210% of high-carbohydrate) liver glycogen deposition (from [14C]glucose) caused by the high-fat diet. The high-fat diet tended to decrease insulin receptor substrate-1 (IRS-1) and phosphatidylinositol-3'-kinase (PI-3-kinase) expression in epididymal fat (26% decrease; P less than 0.1). Englitazone did not reverse this decrease in IRS-1 and PI-3-kinase levels in fat from high-fat-fed rats (there was a further 25-30% decrease, P less than 0.05), nor did it increase PI-3-kinase activity in 3T3-L1 adipocytes under conditions (48 h incubation) where it stimulated 2-DG uptake sixfold or enhanced insulin-stimulated 2-DG uptake. In summary, englitazone prevented the insulin resistance associated with a high-fat diet, but the mechanism of action does not involve changes in fat or muscle glucose transporter content and may not involve activation of the insulin signaling pathway via PI-3-kinase.
Review References:	None
Notes:	Copyright American Diabetes Association. Abstracts are reprinted by the permission of the publisher of the journal for volume, pages, and dates cited. Hypertext links to electronic journal sites, if available, can be found in the the Peer Reviewed Journal List on the IBIDS home page.
Language:	English
Publication Type:	Journal-Article
Keywords:	Adipocytes metabolism : Benzopyrans pharmacology : Dietary Fats administration and dosage : Glucose metabolism : Hypoglycemic Agents pharmacology : Thiazoles pharmacology
URL:	http://www.diabetes.org/Diabetes/