Insulin과 가토식이성동맥경화증과의 관계

Abstract

[한글]

[영문]

Since the discovery of insulin and antibiotics a majority of patients with diabetes were protected against death from diabetic acidosis and infections. They survived much longer than formerly, but still a larger percentage died of vascular lesions. The acceleration influence of diabetes upon atherosclerosis has been known for a long time. And higher incidence of atherosclerosis, coronary diseases, and vascular disease of the kidney among diabetics than nondiabetics was based on the study of autopsy materials (Dragstedt 1945, Best 1948, Clawsen and Bell 1949,

Dolger 1950, Bell 1952).

In recent years, the interest in the problem of human atherosclerosis has veen increased. Since the early observations on atheromatouw lesions in cholesteral fed rabbits, there have been many studies on the possible role of elevated blood cholesterol in the genesis of atherosclerosis (Leary 1941, Dewind et al. 1952, Dragstedt et al. 1954, Keiding et al, 1952, Backer and Selikoff 1952, Duff 1935).

Dragstedt (1945) and Best (1948) drew attention to the significant role of the pancreas in atheroohenesis through its endocrine and exocrine and exocine secretion. Goldengerg et al.(1958) showed high incidence of non-atheromatous sclerosis of small branches of the coronary arteries in diabetic patients, and they interpreted the changes as the result of hypertension which if sfrequently associated with diabetes.

Dewind et al.(1952) found that the average serum cholesterol level was higher in diabetics than non-diabetics but the range was very wide, and no definite correlation was noted between the level of serum cholesterol and the severity of atheroscleriosis. Therefore, the present investigation was undertaken to study the

effects of insulin upon cholesterol-induced atherosclerosis on the assumption that insulin might change atheroma formation.

Materials and Methods

Albino rabbits weighing about 2.0kg. were used and divided into 8 groups as follows:

Group Ⅰ: Six animals for untreated normal controls.

Group Ⅱ: Seven animals for cholesterol feeding.

Group Ⅲ: Six animals for cholesterol feeding after induction of allxan diabetes.

Group Ⅳ: Six animals for combined feeding of cholesterol and insulin after induction of alloxan diabetes.

Group Ⅴ: Six animals for combined feeding of cholesterol and insulin.

Group Ⅵ: seven animals for alloxan controls.

Group Ⅶ: Five animals for insulin treatment after induction of alloxan diabetes.

Group Ⅷ: Six animals for insulin controls.

All animals were fed with about 300gm. of bean-curd residue per animal per day. Cholesterol, 1.5gm per animal per day, was given for 60 and 90days mixed with small amount of bean-curd

residue during fast every morning and full ingestion was confirmed. Alloxan diabetes was induced by intravenous injection of 80mg. of alloxan per kg of body weight and the animals showing fasting blood sugar above 140mg% a week after the alloxan injection were used for the experiment. Insulin was given by intramuscular injection of 1 unit per kg. per animal every other day.

Serum total cholesterol was determined at the 60th and 90th day in all animals by the method of Person (1952). Blood sugar was also determined in all animals by the method of Benedict(1931).

All animals were sacrifice by air embolization at the 60th or 90th day and necropsied. The aortas were examined grossly and microscopically to evaluate the degree of atheroma formation. The coronary artery was examined microscopically to find atherosclerotic changes. And also the kidney was examined for atheromatous change. The liver, adrenals and thyroi were examined for the deposition of lipids, and the pancreas for histological changes in Langerhan's islets.

All tissues were embedded in paraffin after fixation in 4% neutral formalin, and sectioned in 6 microne thickness. All sections were stained with hematoxylin and eoxin, fat stain, best carmine stain, and PAS stain.

Results and Summary

All animals fed cholesterol showed elevation of serum cholesterol but the serum cholesteraol level of insulin plus choleterol groups (Ⅳ and Ⅴ) were lower than those of non-insulin groups (Ⅱ and Ⅲ).

Macroscopic findings of the aortas, particularly in the ascending protein, showed a greater amount of atheromatous change in the animals fed with cholesterol after the induction of alloxan diabetes. The degree of atheroma formation in the animals

fed with cholesterol plus insulin or cholesterol plus insulin after the induction of alloxan diabetes was not greater than those of non-insulin group animals.

Microscopic finding showed that the atheroma formation of the sortas were more in the alloxan diabetes animals fed with cholesterol than in the cholesterol control group.

Coronary arteries showed moderate atheromatous changes mainly in the medium sized branches, and less marked atheromatous changes were observed in the animals fed with cholesterol plus insulin injections.

The liver showed fatty changes in all animals fed with cholesterol but the degree of fatty changes was less marked in the infection insulin animals.

The blood vessels of the kidney showed no atheromatous changes.

The pancreas showed atropy or complete disappearance of β-cells in Langerhan's islets in the animals treated with alloxan.

The other organs showed to notable changes.

In summary, the data obtained by the present investigation showed the alloxan diabetes enhanced cholesterol-induced atherosclerosis in the aortas and coronary arteries, and insulin reduced cholesterol atherosclerosis in the rabbit aorta. The

mechanism by which insulin depresses atheroma formation is not clear.