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Diabetes 52:2539-2545, 2003
© 2003 by the American Diabetes Association, Inc.

Cellular Aspects of Intestinal Lipoprotein Assembly in Psammomys Obesus

A Model of Insulin Resistance and Type 2 Diabetes

Monika Zoltowska1, Ehud Ziv2, Edgard Delvin3, Daniel Sinnett4, Ronny Kalman2, Carole Garofalo1, Ernest Seidman4, and Emile Levy1

1 Department of Nutrition, Centre de Recherche, Hôpital Sainte-Justine, and Université de Montréal, Montréal, Québec, Canada
2 Diabetes Unit, Division of Internal Medicine, Hadassah University Hospital, Jerusalem, Israel
3 Department of Biochemistry, Centre de Recherche, Hôpital Sainte-Justine, and Université de Montréal, Montréal, Québec, Canada
4 Department of Pediatrics, Centre de Recherche, Hôpital Sainte-Justine, and Université de Montréal, Montréal, Québec, Canada

Although postprandial hypertriglyceridemia is a major contributing factor in the development of atherosclerosis, little information is available on the effect of insulin resistance and diabetes on intestinal fat transport. The aim of the present study was to examine intracellular events that govern lipid transport and apolipoprotein (apo) B-48-containing lipoprotein assembly in the small intestine of Psammomys obesus, a model of nutritionally induced insulin resistance and type 2 diabetes. Animals with normoglycemia/hyperinsulinemia and hyperglycemia/hyperinsulinemia exhibited high levels of triglycerides (TGs) in the plasma and intestine and postprandial plasma chylomicrons and apo B-48 compared with normoglycemic/normoinsulinemic animals. In vitro studies, using cultured jejunal explants incubated with either [14C]oleic acid or [35S]methionine, revealed their higher efficiency in de novo TG synthesis, apo B-48 biogenesis, and TG-rich lipoprotein assembly. Accordingly, enhanced monoacylglycerol and diacylglycerol acyltransferase activity was also discernible and concomitant with an increased content of L-fatty acid binding protein and in vivo chylomicron production rates. However, both the I-fatty acid binding protein amount and the apo B-48 proteasomal degradative pathway were decreased. Overall, our findings show 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-lipoproteins, which may contribute to characteristic hypertriglyceridemia.

Address correspondencereprint requests to Dr. Emile Levy, GI-Nutrition Unit, Hôpital Sainte-Justine, 3175 Côte Ste-Catherine Rd., Montreal, Quebec H3T 1C5, Canada. E-mail: levye{at}justine.umontreal.ca


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