Toxicological Sciences, Vol 50, 146-151, Copyright © 1999 by Society of Toxicology
CE Herrman, RA Sanders, JE Klaunig, LR Schwarz and JB Watkins 3rd
Insulin-dependent diabetes mellitus in both humans and animals leads to
structural and functional changes including hepatomegaly. This study
examined hypertrophy, hyperplasia, and apoptosis, three basic aspects of
tissue growth, in livers of Sprague-Dawley and Wistar rats made diabetic by
iv injection of streptozotocin 8, 30, or 90 days previously.
Immunohistochemical measurement of proliferating cell nuclear antigen
revealed that hepatic DNA labeling indices were similar in normal control
animals and diabetic rats 30 or 90 days post diabetic induction, but were
reduced to 45 to 50% of control in insulin-treated diabetic animals,
perhaps due to altered receptor activity or to partial insulin resistance,
as reported previously. Flow cytometry indicated a 613% increase in diploid
hepatocytes in the livers of diabetic rats 30 days after the onset of
diabetes, compared to control. Diabetic livers contained 29% fewer
tetraploid cells, 81% fewer octaploid cells, and 20% more binucleated
hepatocytes than normal controls. At 90 days, the overall smaller size of
hepatocytes in diabetic tissue was evidenced by more cells per area.
Insulin treatment prevented some of these changes, but did not restore
ploidy to a normal distribution. Mitosis, while 300% of normal at 8 days
after streptozotocin injection, was reduced to 25% of normal after 90 days
of diabetes. The morphological evidence of apoptosis was decreased by 23%
to 76% in the diabetic liver, and was reversed but not normalized by
insulin treatment. This study indicates that the hepatomegaly observed in
streptozotocin-induced experimental diabetes may be due primarily to early
hyperplasia, and later decreased apoptosis.
ARTICLES
Decreased apoptosis as a mechanism for hepatomegaly in streptozotocin- induced diabetic rats
Medical Sciences Program, Indiana University School of Medicine, Bloomington 47405-4201, USA.
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