title: Hyperlipidemia and atherosclerosis in experimental insulinopenic diabetic monkeys.
abstract: Chronic insulinopenic diabetes was induced by i.v. streptozotocin in the non-human primate Macaca fuscata. Five diabetic monkeys were kept for 8-19 months and nine for 24-48 months without any insulin treatment. Hyperglycemia (241 +/- 22 mg/dl, M +/- SE less than or equal to 1 year) progressed to 376 +/- 34 mg/dl (greater than 2 years) and ketosis to 3.5 mM (greater than 2 years) during the course of diabetes; this was roughly inversely proportional to hypoinsulinemia (3.4 microU/ml, 2 years). Serum cholesterol increased from 184 +/- 11 (less than or equal to 1 year) to 328 +/- 66 mg/dl (greater than 2 years) with the major increase in LDL-cholesterol (2.7-fold over control, greater than 2 years). HDL-cholesterol did not change at all throughout the experimental period. TG increased from 144 +/- 25 (less than or equal to 1 year) to 676 +/- 116 (greater than 2 years) with a major increase in the VLDL fraction (15-fold over control, greater than 2 years). Serum levels of apo B increased to 141 +/- 16 (less than or equal to 2 years) and 223 +/- 8 mg/dl (greater than 2 years) in contrast to control, 73 +/- 2. Morphologically, lipid deposition in the intima and fatty streaks have been observed in the abdominal aorta of all the diabetic monkeys with duration of more than 2 years. In six of the diabetic monkeys atheromatous changes such as intimal and medial thickening with smooth muscle cell proliferation were observed with foam cell formation. Similar atherosclerotic lesions were observed in renal and coronary arteries in at least six of these monkeys. In diabetic monkeys with duration of less than 2 years, mild atherosclerotic lesions were observed in two out of five. The results indicate that long standing insulinopenia leads to metabolic derangements characterized by hyperglycemia, ketonemia and hyperlipidemia. Elevation of LDL-cholesterol and VLDL TG with an increase of apo B is a characteristic of lipoprotein disorder. Morphologically, early to moderately advanced lesions of atherosclerosis were observed in aorta, renal and coronary arteries as a result of metabolic derangement due to insulin deficiency.
authors.affiliation: Third Department of Medicine, Shiga University of Medical Science, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Harano
authors.forename: H
authors.initials: H
authors.lastname: Kojima
authors.forename: K
authors.initials: K
authors.lastname: Kosugi
authors.forename: M
authors.initials: M
authors.lastname: Suzuki
authors.forename: M
authors.initials: M
authors.lastname: Harada
authors.forename: T
authors.initials: T
authors.lastname: Nakano
authors.forename: H
authors.initials: H
authors.lastname: Hidaka
authors.forename: A
authors.initials: A
authors.lastname: Kashiwagi
authors.forename: R
authors.initials: R
authors.lastname: Torii
authors.forename: Y
authors.initials: Y
authors.lastname: Taniguchi
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000473:pathology / Q000648:ultrastructure; D001161:Arteriosclerosis / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D002784:Cholesterol / Q000097:blood; D003331:Coronary Vessels / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006949:Hyperlipidemias / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D007328:Insulin / Q000097:blood; D007657:Ketone Bodies / Q000097:blood; D007668:Kidney / Q000473:pathology* / Q000648:ultrastructure; D008055:Lipids / Q000032:analysis; D008074:Lipoproteins / Q000097:blood; D008251:Macaca; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000473:pathology* / Q000648:ultrastructure; D009206:Myocardium / Q000473:pathology* / Q000648:ultrastructure; D012016:Reference Values; D012077:Renal Artery / Q000473:pathology / Q000648:ultrastructure; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
chemical_list: D005230:Fatty Acids, Nonesterified; D007328:Insulin; D007657:Ketone Bodies; D008055:Lipids; D008074:Lipoproteins; D014280:Triglycerides; D002784:Cholesterol