Repeatedly-bred rats develop arteriosclerosis, hyperlipidemia, hyperglycemia and other degenerative changes, spontaneously. An injection of alloxan (10 mg./100 gm. body weight, subcutaneously, eighteen-hours postfasting) given to healthy, virgin and to arteriosclerotic and diabetic breeder rats caused severe ketosis, hyperglycemia, hyperlipidemia and fatty metamorphosis of the liver. Animals were sacrificed daily for one week and after the fourth and eighth week of severe, untreated diabetes.
The previously arteriosclerotic rats showed the greater catabolic and pathophysiologic changes. Many animals died on the third day postalloxan with massive fatty metamorphosis of the liver. At this time, adrenal and thymus gland weights, serum enzymes, e.g., SGOT, SGPT and LDH, serum lipids, e.g., free fatty acids, triglycerides and cholesterol, serum corticosterone and urinary 17-ketosteroids, as well as chemical analyses of hepatic lipids, e.g., total lipids, trigly- ceride and cholesterol, all reflected the severe insulin deficiency.
Eventually, the severity of these pathophysiologic changes subsided. Approximately half of the animals became emaciated with milky serum containing high levels of glucose and lipids. These animals were ketotic, their beta cells were agranular and they were severely arteriosclerotic. Remaining animals were “obese,” with fatty livers but normal-appearing serum containing less glucose and lipid than their emaciated counterparts. These “obese” diabetic rats had less severe ketosis, partially degranulated beta cells and regression of their arteriosclerosis. This dichotomous response to severe diabetes may be due to the partial recovery of beta cells of some animals concomitant with partial correction of defective lipid and carbohydrate metabolism.