Summary: Chronic insulinopenic diabetes was induced by i.v. streptozotocin in the non- human primate Macaca fascicularis. Six diabetic monkeys were kept for 8 – 19 months and six for 24 – 48 months without any insulin treatment. Hyperglycemia (236 ± 22 mg/dL) progressed to 368 ± 33 mg/dL and ketosis to 3.5 mM during the course of diabetes; this was roughly inversely proportional to hypoinsulinemia (3.3 μU/mL). Serum cholesterol increased from 180 ± 11 to 321 ± 65 mg/dL with the major increase in LDL-cholesterol (2.7-fold over control). HDL-cholesterol did not change at all throughout the experimental period. TG increased from 141 ± 24 to 662 ± 114 with a major increase in the VLDL fraction (15-fold over control). Serum levels of apo B increased to 132 ± 12 and 199 ± 8 mg/dL in contrast to control, 68 ± 2. Morphologically, lipid depositions 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 athermanous 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 six. The results indicate that long standing insulinopenic leads to metabolic derangements characterized by hyperglycemia, ketonemia and hyperlipidemia. Elevation of LDL-cholesterol and VLDL TG with an increase of apo B is 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.
Materials and Methods: Twelve monkeys (Macaca fascicularis) at 3 ± 2 years weighing 2.7 – 4.2 kg were injected with streptozotocin (50 mg/kg, Sigma) dissolved in 0.1 M citrate buffer (pH 4.2) intravenously. Control monkeys were injected with citrate buffer alone. The Macaca fascicularis are mature at age 3 – 4 years, and the control monkeys were in general free from atherosclerotic lesions up to 3 – 5 years. The chow contains by weight 26.5% protein, 6.8% fat, 1.5% fiber and 50.4% carbohydrate other than vitamins and essential elements. They gradually lost weigh during the observation period. Blood was obtained for the saphenous vein after anesthesia with Ketaral (0.1 mL/kg/BW). All of monkeys given water ad libitum.
Conclusion: Hyperlipidemia characterized by elevated LDL, apo B and VLDL is postulated to play an important role. Coexisting insulinopenia in itself also seems to accelerate the initiation or progression of diabetic macroangiopathy.
