The Effect of Insulin upon the Ketone Metabolism of Normal and Diabetic Cats*

Until recently the views prevalent in the literature with respect to ketone formation in the normal and diabetic organism were as follows: The long fatty acid carbon chains are split by successive /3 oxidation, 2 carbons at a time, with the formation of intermediate shorter fatty acids and acetic acid (Knoop hypothesis). Normally this process continues to completion, but in the absence of sufficient carbohydrate stores (fasting), or without insulin as an obligatory carbohydrate catalyst (diabetes), the process stops at the 4-carbon ketone stage. Each molecule of fatty acid gives rise to 1 molecule of ketone. An obligatory chemical coupling of the oxidation of carbohydrate and ketones was assumed. Failing carbohydrate oxidation, ketones cannot be utilized by the peripheral tissues; hence they are excreted in toto. Ketone Utilization by Peripheral Issues---Since 1928, however, considerable evidence has accumulated in the literature, necessitating complete revision of these concepts. For example, Snapper and Gruenbaum (1928), in perfusion experiments on striated muscle of normal animals, found a considerable disappearance of circulating ketones. Chaikoff and Soskin (1928), from a study of the rate of disappearance of ketones from the blood following injection of acetoacetate, concluded that ketones are utilized by the muscles of the diabetic as well as the normal eviscerated dog. Later Friedemann (1936) and Mirsky and Broh-