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International Journal of Experimental Diabetes Research
Volume 1, Issue 3, Pages 203-210
http://dx.doi.org/10.1155/EDR.2000.203

The Relationship Between Cholesterol Absorption and Intestinal Cholesterol Synthesis in the Diabetic Rat Model

1Department of Clinical Medicine, Trinity College Dublin, Ireland
2Department of Biochemistry, Royal College of Surgeons in Ireland, Ireland
3The Adelaide and Meath Hospital, Dublin, Ireland

Accepted 14 December 1999

Copyright © 2000 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The chylomicron remnant particle is thought to be particularly atherogenic and we have previously shown alterations in post-prandial lipoproteins which could contribute to their atherogenicity. Cholesterol metabolism is disturbed in diabetes, yet the effect of diabetes on intestinal cholesterol synthesis and absorption has rarely been investigated. The aim of this study was to examine cholesterol absorption and intestinal synthesis of cholesterol in the streptozotocin diabetic rat. Twelve diabetic rats were paired with 12 control rats. [C14]-Cholesterol emulsion was administered and the lymph duct was canulated. Lymph was collected for 4 h. At sacrifice blood was taken for plasma lipoprotein measurements. Chylomicrons were prepared from the lymph by ultracentrifugation and [C14]-cholesterol content was determined by liquid scintillation counting. Lymph apolipoprotein B48 was isolated by gradient gel electrophoresis, and quantified by densitometric scanning. Serum triglyceride and cholesterol were greatly elevated in diabetic compared to control animals (260 ± 90 and 9.8 ± 8.0 mg/ml vs. 1.0 ± 0.4 and 0.6 ± 0.3 mg/ml, p < 0.0001 respectively). Lymph chylomicron apo B48 was similar in the two groups. Cholesterol absorption was not significantly different in diabetic compared to control rats but cholesterol synthesis was significantly, higher in the diabetic animals (550 ± 352 vs. 322 ± 113 μg/h p < 0.03). There was a positive correlation between apo B48 and cholesterol absorption (r = 0.70, p < 0.01) in the diabetic rats and control rats (r = 0.71, p < 0.01) but no correlation between apo B48 and cholesterol synthesis in either group. This study demonstrates that cholesterol synthesis was increased in diabetes whereas cholesterol absorption was unaffected suggesting that intestinal cholesterol synthesis made an important contribution to the hypercholesterolaemia seen in the diabetic animals.