The Effect of Alloxan Diabetes on Experimental Cholesterol Atherosclerosis in the Rabbit

Abstract

In a previous publication in this series, Duff and McMillan (1) made a comparison of the effects of cholesterol feeding in normal rabbits and in rabbits rendered persistently diabetic by means of alloxan. It was found that in the two groups of animals hyperchotesterolemia of comparable degree was induced b y the feeding procedure. Nevertheless, the severity of the atherosclerosis of the aorta produced in the diabetic rabbits was much less than in the non-diabetic controls. Only two factors were observed to be consistently associated with this inhibition of the expected morphological effects of cholesterol feeding; namely, the diabetic state and a degree of visible lipemia considerably greater than that observed in the control animals. Because of the occurrence of this greater degree of visible lipemia in the diabetic rabbits, it was thought likely that a study of the main serum lipids, rather than of cholesterol alone, might serve to elucidate the mechanJ.qm of the inhibition of cholesterol atherosclerosis in the alloxan-diabetic rabbit. In this paper, such a study is presented. The findings have already been briefly recorded (2).The llpids of the serum are insoluble in water; nevertheless they are present in the blood serum, an aqueous medium, which normally is clear and limpid. It is obvious, therefore, that there must be some mechanism whereby they are held in suspension in the serum. It is equally obvious that, when this mechanism becomes upset to a greater or lesser degree, then the colloidal stability of the lipids in the serum is impaired. From the study of the lipids in both normal and pathological sera, it has become evident that the serum lipids, as a group, exhibit two important features. In the first place, the different lipid components are known to show an interrelationship which is more constantly maintained and, therefore, of more significance than the concentration of any single component (3). Secondly, there exists a close association between the * This work was assisted by grants-in-aid from the National

Atherosclerosis and myocardial ischemic lesions in alloxan-diabetic rabbits fed a low cholesterol diet.

“…17 The cholesterol/phospholipid ratio was elevated in diabetic rabbits in this experiment, but the ratio was lower in diabetic rabbits fed much larger amounts of cholesterol. 4 Higher cholesterol/phospholipid ratios are usually associated with more extensive atherosclerosis. 4 The alloxan-nondiabetic rabbits provided a control group for the possible toxic effects of alloxan, aside from its effect as a diabetogenic agent.…”

“…4 Higher cholesterol/phospholipid ratios are usually associated with more extensive atherosclerosis. 4 The alloxan-nondiabetic rabbits provided a control group for the possible toxic effects of alloxan, aside from its effect as a diabetogenic agent. In general, the degree of atherosclerosis in alloxan-nondiabetic rabbits was similar to that of the nonalloxanized controls.…”

“…1 -3 Serum phospholipid concentrations are also increased in cholesterol-fed diabetic rabbits but there is a reduction in the cholesterol/phospholipid ratio, 4 and the Sf 12-30 lipoproteins. 5 Although cholesterol-fed diabetic rabbits develop atherosclerotic lesions, there is a paradoxical decrease in the extent of disease unless insulin therapy is instituted, and then the degree of atherosclerosis in the diabetic rabbits is increased to the level found in the nondiabetic rabbits.…”

Diabetes and atherosclerosis: is there a role for hyperglycemia?

“…Early studies in rabbits made diabetic by the administration of alloxan resulted in marked hypertriglyceridemia, which confounded the effect of the diabetes on atherosclerosis (19). Moreover, diabetic nonhuman primates have not provided much insight into the role of glucose in the pathogenesis of atherosclerosis (20).…”

Diabetic Vascular Disease

“…Although it is expected that diabetes should increase atherosclerosis, the extrapolation of the human disease 67 used alloxan to produce diabetes in cholesterol-fed rabbits. In a seemingly paradoxical result, the diabetic rabbits had less atherosclerosis.…”