Hypertriglyceridemia is often associated with insulin-dependent diabetes and may be manifested as hyperchylomicronemia and/or elevated levels of very low density lipoproteins (VLDL). This is largely due to defective clearance of these particles from the circulation, and may be a function of modified lipoprotein lipase activity and/or alterd apolipoprotein composition of these transport particles. Both alterations have been observed in experimental diabetes in rats. However, it is unclear as to whether the apoprotein alterations are a result of altered metabolism and secretion by the liver (VLDL) or intestine (chylomicrons) or is due to modified post-secretory metabolism of these particles. The objectives of this proposal are to assess the relative contribution of liver and intestine to the abnormal apolipoprotein composition of triglyceride-containing transport particles. The intestinal contribution will be assessed by analysis of mesenteric lymph of diabetic rats in which hepatic secretion is minimized with ethinyl estradiol. Modifications in hepatic contribution of apolipoproteins in diabetes will be determined by liver perfusion in situ, and by analysis of plasma of diabetic rats in which mesenteric lymph contributions have been eliminated. Analysis of lipid and apoprotein concentration and composition of transport particles in these models should allow an accurate assessment of altered hepatic and intestinal lipoproteins synthesis and secretion in experimental diabetes.
