Studies of the development of diabetic ketosis in the rat

Plasma glucose, free fatty acid, ketone, and triglyceride concentrations were measured at frequent intervals after the administration of alloxan to rats. Hepatic triglyceride levels were determined in the same animals. During the second 24-hr period after alloxan administration, severe ketoacidosis developed and triglyceride concentrations in the liver became markedly elevated. This finding was incompatible with the thesis that enhanced ketogenesis under circumstances of increased free fatty acid delivery to the liver requires diminished triglyceride synthesis. Plasma insulin and glucagon concentrations were determined at each time point. Initial changes in plasma glucose, ketones, free fatty acids, and triglycerides were accompanied by a fall in insulin concentrations, but no change occurred in glucagon levels. However, concentrations of the latter hormone increased dramatically in the second 24 hr after alloxan treatment and probably contributed to the development of the extreme hyperglycemia observed during this time period.