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O0076 ROLE OF THE SMALL INTESTINE IN DYSLIPIDEMIA DURING THE DEVELOPMENT OF INSULIN RESISTANCE IN PSAMMAMYS OBESUS

Levy, E. H.1; Seidman, E. G.2; Zoltowska, M.1; Delvin, E.3; Sinnett, D.2; Kalman, R.4; Ziv, E.4

Journal of Pediatric Gastroenterology and Nutrition: June 2004 - Volume 39 - Issue - p S36-S37
ABSTRACTS: Oral Presentation Abstracts
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1Nutrition,2Pediatrics,3Biochemistry, Centre de Recherche, Hôpital Ste-Justine, Montréal, Canada,4Diabetes Unit, Division of Internal Medicine, Hadassah University Hospital, Jerusalem, Israel

Submitted by: sspahis@justine.umontreal.ca

Introduction: The occurrence of nutrition-induced insulin resistance and diabetes in the sand rat Psammomys obesus animal model mimics that of human populations emerging from a food-scarce environment into nutritional affluence inappropriate for human metabolic capacity. Recently, we demonstrated that the development of an insulin-resistant/diabetic state in Psammomys obesus triggers the whole intra-enterocyte machinery,leading to lipoprotein assembly and favoring the intestinal oversecretion of apo B-48-containing lipoproteins during fat feeding.

Methods: The aim of the present study was to examine whether the small intestine can increase triglyceride-rich lipoprotein secretion under fasting and insulin resistance conditions. Studies were carried out on normoglycemic-normoinsulinemic animals as well as normoglycemic-hyperinsulinemic and hyperglycemic-hyperinsulinemic animals.

Results: Acute elevation of long-chain fatty acids following the infusion of intralipid and heparin enhanced free fatty acid influx through the basolateral membrane of the enterocyte in insulin-resistant, compared to normal animals (p<0.05). This resulted in the overproduction of apo B-48, lipid esterification and TG-rich lipoprotein synthesis (p<0.05). Concomitant with the raised lipogenesis observed in the insulin-resistant animals, there was an elevation of lipogenic enzymes, including malic enzymes, fatty acid synthase and acetyl-CoA carboxylase. Improved insulin sensitivity in Psammomys obesus rats by treatment with rosiglitazone, a peroxisome proliferator-activated receptor-gamma agonist and insulin sensitizer, tended to normalize most of lipid aberrations.

Conclusion: Our findings suggest that decreased insulin sensitivity of the small intestine may contribute to hyperlipidemia that characterizes insulin-resistant and diabetic animals.

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Reference(S):

*Zoltowska M, Ziv E, Delvin E, and al.Cellular Aspects of Intestinal Lipoproteins Assembly in Psammomys obesus,A Model of Insulin Resistance and type 2 Diabetes. Diabetes 2003;52:2539–45
    *Zoltowska M, Ziv E, Delvin E, and al.Both Insulin Resistance and Diabetes in Psammomys obesus Upregulate the Hepatic Machinery Involved in Intracellular VLDL Assembly. ATVB 2003 (In press)
      *Haidari M, Leung N, Mahbub F, and al.Fasting and postprandial overproduction of intestinally derived lipoproteins in an animal model of insulin resistance. Evidence that chronic fructose feeding in the hamster is accompanied by enhanced intestinal de novo lipogenesis and ApoB48-containing lipoprotein overproduction. J Biol Chem. 2002;277:31646–55
        © 2004 Lippincott Williams & Wilkins, Inc.