Effect of hypocholesterolemia on cholesterol synthesis in small intestine of diabetic rats
Studies by our and other laboratories have demonstrated that cholesterol synthesis is increased in the small intestine of insulinopenic diabetic animals. In normal animals, many factors have been shown to regulate cholesterol synthesis in the small intestine, including changes in plasma cholesterol levels. The purpose of this study was to determine the effect of lowering plasma cholesterol levels on small intestine cholesterol synthesis in streptozocin-induced diabetic rats. In diabetic rats, 4-aminopyrazolo(3,4-d)pyrimidine (4-APP)-induced hypocholesterolemia (plasma cholesterol levels less than 20 mg/dl) resulted in a 2.5-fold increase in small intestine cholesterol synthesis, which was most marked in the distal small intestine, decreasing proximally. In the distal small intestine the incorporation of /sup 3/H/sub 2/O into cholesterol was 0.28 +/- 0.04 mumol.h-1.g-1 in diabetic rats versus 1.60 +/- 0.38 in diabetic rats administered 4-APP (P less than .01). This stimulation of cholesterol synthesis occurred in the upper villus, middle villus, and crypt cells isolated from the middle intestine of the 4-APP-treated diabetic animals. In agreement with these observations, functional hypocholesterolemia due to Triton WR-1339 administration also stimulated cholesterol synthesis 2.5-fold in the small intestine of normal and diabetic animals. In the distal small intestine, cholesterol synthesis was 0.43 +/- 0.10 mumol.h-1.g-1 in the diabetic rats versus 1.08 +/- 0.21 in diabetic rats treated with Triton WR-1339 (P less than .05). In both the 4-APP and Triton WR-1339 experiments, the response of the diabetic rats was similar to that observed in normal rats.
- Research Organization:
- Univ. of California, San Francisco
- OSTI ID:
- 5666534
- Journal Information:
- Diabetes; (United States), Vol. 36:11
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
CHOLESTEROL
BIOSYNTHESIS
DIABETES MELLITUS
PATHOGENESIS
ALKALINE PHOSPHATASE
FASTING
IN VITRO
RATS
SMALL INTESTINE
TRITIUM COMPOUNDS
ANIMALS
BODY
DIGESTIVE SYSTEM
DISEASES
ENDOCRINE DISEASES
ENZYMES
ESTERASES
GASTROINTESTINAL TRACT
HYDROLASES
HYDROXY COMPOUNDS
INTESTINES
LABELLED COMPOUNDS
MAMMALS
METABOLIC DISEASES
ORGANIC COMPOUNDS
ORGANS
PHOSPHATASES
RODENTS
STEROIDS
STEROLS
SYNTHESIS
VERTEBRATES
550901* - Pathology- Tracer Techniques