ATTEMPTS TO PRODUCE DIABETES IN GUINEA PIGS BY ALLOXAN AND PANCREATECTOMY With Observations on the Effect of a Diet Deficient in Cystine and Methionine

Abstract

Guinea pigs developed temporary diabetes with hyperglycemia and glycosuria of several days'' duration following the daily intraven. admn. of alloxan in dosage of 100-300 mg./kg. Permanent diabetes could not be produced because of the narrow margin between the diabetogenic dose and that which produced marked anemia and fatal kidney damage. Guinea pigs tolerated large doses of alloxan intraperit. There was an initial hyper-glycemic phase but no diabetes or kidney lesions. When 180 mg./kg. was given intraven., marked hypoglycemia was observed within a few hrs. but no subsequent diabetes. The animals died within 5 days with severe hemolytic anemia, degenerative lesions of the pancreatic islets, and necrosis of the kidney tubules. When the same dose was given intraven. in 3 parts at 5-min. intervals, initial hyperglycemia was the predominant feature and the animals survived without hypoglycemia or diabetes. The blood of normal guinea pigs had an avg. reduced glutathione concn. of 59 mg. per 100 cc, which is higher than that of rabbits, rats or humans. The concn. was decreased immediately after alloxen injn. After a diet deficient in cystine and methionine, severe hypoglycemia usually occurred within 6 hrs. after food was withdrawn. Only 2 animals had a lowered blood glutathione without this fasting hypoglycemia, and these responded as normal animals to the intraperit. injn. of alloxan.