Transgenic mice expressing ifn-[gamma] in the pancreatic beta cells
are resistant to streptozotocin-induced diabetes.
Gu, Danling, Marc Arnush, Stephen P. Sawyer, and Nora Sarvetnick.
Department of Neurophamacology CVN-10, The Scripps Research
Institute, La Jolla, California 92037
APStracts 2:0144E, 1995.
Gu, Danling, Marc Arnush, Stephen P. Sawyer, and Nora Sarvetnick. In
28 adult Ins-IFN-[gamma] transgenic mice, injection of high doses of
streptozotocin (STZ-first injection, 300 [mu]g/g body weight; second
injection, 200 [mu]g/g body weight 4 hr later) failed to induce
severe hyperglycemia. To the contrary, 28 BALB/c mice developed
diabetes mellitus after identical injections of STZ. Because the STZ
-induced islet damage was partially inhibited in Ins-IFN-[gamma]
transgenic mice, their glycemia levels became normal 4 days after STZ
administration. Both transgenic and BALB/c mice lost weight after
receiving STZ, but the body weights of transgenic mice then returned
to pre-treatment levels in a nearly parallel manner with the
glycemia. Immunolabeling with insulin, identified an unusual
spreading pattern of insulin immunoreactivity. Ultrastructural
observations confirmed that [beta] cell necrosis and degranulation
were more severe in STZ-treated BALB/c than in Ins-IFN-[gamma]
transgenic mice. Moreover, regeneration of pancreatic duct cells and
islet neogenesis were observed in the transgenic mice. Therefore,
after STZ treatment, the Ins-IFN-[gamma] transgenic mice apparently
were resistant to the induction of severe diabetes, whereas their
BALB/c age-matched counterparts succumbed to the disease.
Received 24 May 1995; accepted in final form 29 June 1995.
APS Manuscript Number E232-5.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 18 July 1995.