Pathophysiologic responses to severe, chronic alloxan diabetes in arteriosclerotic and non-arteriosclerotic rats

  • B.C. Wexler
    Address of the author: Dr. Bernard C. Wexler, Director, May Institute for Medical Research, 421 Ridgeway Avenue, Cincinnati, Ohio 45229 U.S.A.
    May Institute for Medical Research of the Jewish Hospital and Departments of Pathology and Medicine, University of Cincinnati, College of Medicine, Cincinnati, Ohio 45229 U.S.A.
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  • Author Footnotes
    1 Dr. Wexler is supported by a Research Career Award Grant (HE-K3-1734), from the National Heart Institute, NIH, U.S. Public Health Service.
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      Repeatedly bred rats develop arteriosclerosis, hyperlipidemia, hyperglycemia and other degenerative changes, spontaneously. An injection of alloxan given to non-arteriosclerotic virgin and to arteriosclerotic and diabetic breeder rats caused severe ketosis, hyperglycemia, hyperlipidemia, marked alterations in serum enzymes and alterations in adrenal secretory activity. After two months, half of all of the diabetic animals were obese with little or no arteriosclerosis, the remaining half were emaciated with severe arteriosclerosis. This condition of obesity or emaciation persisted throughout the course of the experiment. This dichotomous response was ascribed to differences in beta cell recovery from alloxan. Treatment was deliberately withheld and the diabetes allowed to run unchecked until the animals began to die in great numbers, i.e., only 52 animals survived of a total of 2000. After 5 months of unrelenting diabetes, the severity of hyperglycemia lead become slightly reduced, adrenal function was definitely compromised, hyperlipidemia persisted except for cholesterol, serum transaminases (SGOT and SGPT) were greatly elevated but LDH was surprisingly reduced, and all subjects were hypercalcemic. All of the animals were blind and most of the obese subjects expired but the emaciated and arteriosclerotic animals survived. The formerly healthy virgin subjects had also developed blindness and advanced arteriosclerosis during the 5 months of unrelenting diabetes.


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