The Mechanism of alloxan protection in experimental Atherosclerosis – COOK (1953)

D. L. COOK, LOIS M. MILLS, and D. M. GREEN

The Mechanism of alloxan protection in experimental Atherosclerosis

J Exp Med. 1954 Feb;99(2):119-24.
pubmed

Summary: Experiments were performed to compare the effects of cholesterol feeding in (a) control rabbits, (b) alloxan-diabetic rabbits, and (c) rabbits injected with alloxan while the pancreas was temporarily occluded from the circulation.

Results: The alloxan-diabetic rabbits consumed significantly higher quantities of cholesterol and food and had serum cholesterol and lipoprotein concentrations significantly increased over the control levels. They failed to show a commensurate increase in the degree of atherosclerosis. Rabbits in which the diabetogenic action of alloxan was prevented by temporary occlusion of the pancreas from the circulation during its administration developed grades of hypercholesterolemia, hyperlipoproteinemia, and atherosclerosis not significantly different from the controls.

We reckon: We’ve known, since the work of Russian scientist Nikolay Anichkov in 1913, that rabbits fed cholesterol rapidly become atherosclerotic and develop cardiovascular disease in a linear relationship – the more cholesterol they ate the faster they became atherosclerotic (unlike humans).

In 1949 it was discovered (Duff & McMillan “The effect of alloxan diabetes on experimental cholesterol atherosclerosis in the rabbit” ) that Rabbits exposed to the chemical alloxan became rapidly diabetic, but they appeared to be protected against the progression of atherosclerosis when fed cholesterol.

This study (Cook – 1953) showed that it was only the absence of insulin in the diabetic animals that protected them against atherosclerosis in an otherwise highly atherosclerotic milieu.  In other words insulin is necessary for blood vessels to become atherosclerotic.

And Cruz – 1961 shows that insulin actually causes atherosclerosis.