Diabetes mellitus is associated with an increased risk of atherosclerosis that may be associated with alterations in lipid metabolism. The overall objective of this study is to determine the effects of experimentally-induced diabetes mellitus on very-low-density-lipoprotein (VLDL) metabolism in the rat. In order to accomplish this objective, the following specific aims will be pursued: 1) Clearance of 125I-VLDL apolipoproteins by diabetic and control rats will be measured in vivo and in isolated liver perfusions. In particular, the presence or absence of selective clearance of either of the predominant forms of apolipoprotein B will be determined. 2) The involvement of insulin and thyroid hormones in the control of apolipoprotein clearance in diabetics will be investigated. 3) The degree of glycosylation of apolipoproteins from diabetic animals will be measured, and the effects of glycosylation on apolipoprotein clearance will be determined. 4) Activity of lipoprotein lipase and hepatic lipase will be measured in diabetic rats. The effects of glycosylation of apolipoproteins on lipoprotein lipase and hepatic lipase activities will be investigated. The model of diabetes to be used in these experiments will be the streptozotocin-diabetic rat. Diabetes will be induced by injection of streptozotocin at a dose of 65 mg/kg body weight. Rats will be maintained on insulin for one week in order to minimize direct toxic effects of streptozotocin, then insulin will be withdrawn for at least 3 days prior to any experimental procedures.
| Garber, D W; Venkatachalapathi, Y V; Gupta, K B et al. (1992) Turnover of synthetic class A amphipathic peptide analogues of exchangeable apolipoproteins in rats. Correlation with physical properties. Arterioscler Thromb 12:886-94 |
