TY - JOUR
T1 - Suppression of apoptosis is responsible for increased thickness of intestinal mucosa in streptozotocin-induced diabetic rats
AU - Noda, Takahiro
AU - Iwakiri, Ryuichi
AU - Fujimoto, Kazuma
AU - Yoshida, Toshifumi
AU - Utsumi, Hiroyoshi
AU - Sakata, Hiroyuki
AU - Hisatomi, Akitaka
AU - Aw, Tak Yee
N1 - Funding Information:
From the Department of Internal Medicine, Saga Medical School, Nabeshima, Saga, Japan; and the Department of Physiology, Louisiana State University Medical Center, Shreveport, LA. Submitted July 19, 1999; accepted October 2, 2000. Supported by Grant-in-Aid from the Ministry of Education in Japan for Scientific Research No. 10470137 (to K.F.) and No. 10670487 (to R.I.). Address reprint requests to Kazuma Fujimoto, MD, Professor and Head, Department of Internal Medicine, Saga Medical School, 5-1-1 Nabeshima, Saga, 849-8501, Japan. Copyright © 2001 by W.B. Saunders Company 0026-0495/01/5003-0014$35.00/0 doi:10.1053/meta.2001.21030
PY - 2001
Y1 - 2001
N2 - Intestinal mucosal growth is a common, but uncharacterized, observation associated with diabetes mellitus. Epithelial homeostasis is balanced by regulation of cell proliferation and cell death. To determine the contribution of apoptosis to the overall maintenance of intestinal growth, we examined intestinal apoptosis in the well-characterized streptozotocin (STZ)-induced diabetes rat model. Rats were injected with STZ (75 mg/kg body weight), thereafter they were allowed free feeding or restricted feeding for 3 weeks. Food intake and intestinal mucosal height were evaluated. In a second experiment, additional groups of animals were injected with STZ and were fed ad libitum for 1 or 3 weeks. Ornithine decarboxylase (ODC) activity, ratio of fragmented DNA to total DNA, electrophoresis of fragmented DNA, and Western blot analysis of caspase-3 were examined. Food intake gradually increased in free-feeding rats after induction of diabetes. Intestinal mucosal height in free-feeding diabetic rats was approximately 25% longer than controls, but this increase in mucosal height was not observed in restricted-fed diabetic rats (25 g/d). ODC activity in intestinal mucosa in diabetic rats did not differ from that of control rats. Percent fragmented DNA of diabetic rats 1 week after STZ injection was significantly lower than that of control rats, and this decrease returned to the control level 3 weeks after STZ treatment. Active form of caspase-3 was attenuated 1 week after drug treatment. Attenuated effect of diabetic rats on intestinal apoptosis did not affect increased apoptosis after ischemia-reperfusion. Suppression of apoptosis in the early days of STZ-induced diabetes was responsible for the increased mucosal height in the small intestine in STZ-induced diabetic animals.
AB - Intestinal mucosal growth is a common, but uncharacterized, observation associated with diabetes mellitus. Epithelial homeostasis is balanced by regulation of cell proliferation and cell death. To determine the contribution of apoptosis to the overall maintenance of intestinal growth, we examined intestinal apoptosis in the well-characterized streptozotocin (STZ)-induced diabetes rat model. Rats were injected with STZ (75 mg/kg body weight), thereafter they were allowed free feeding or restricted feeding for 3 weeks. Food intake and intestinal mucosal height were evaluated. In a second experiment, additional groups of animals were injected with STZ and were fed ad libitum for 1 or 3 weeks. Ornithine decarboxylase (ODC) activity, ratio of fragmented DNA to total DNA, electrophoresis of fragmented DNA, and Western blot analysis of caspase-3 were examined. Food intake gradually increased in free-feeding rats after induction of diabetes. Intestinal mucosal height in free-feeding diabetic rats was approximately 25% longer than controls, but this increase in mucosal height was not observed in restricted-fed diabetic rats (25 g/d). ODC activity in intestinal mucosa in diabetic rats did not differ from that of control rats. Percent fragmented DNA of diabetic rats 1 week after STZ injection was significantly lower than that of control rats, and this decrease returned to the control level 3 weeks after STZ treatment. Active form of caspase-3 was attenuated 1 week after drug treatment. Attenuated effect of diabetic rats on intestinal apoptosis did not affect increased apoptosis after ischemia-reperfusion. Suppression of apoptosis in the early days of STZ-induced diabetes was responsible for the increased mucosal height in the small intestine in STZ-induced diabetic animals.
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U2 - 10.1053/meta.2001.21030
DO - 10.1053/meta.2001.21030
M3 - Article
C2 - 11230775
AN - SCOPUS:0035079137
SN - 0026-0495
VL - 50
SP - 259
EP - 264
JO - Metabolism: Clinical and Experimental
JF - Metabolism: Clinical and Experimental
IS - 3
ER -
