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ORIGINAL RESEARCH ARTICLE

Suppression of Intestinal Mucosal Apoptosis by Ghrelin in Fasting Rats

Jae Myung Park^*,,1, Takashi Kakimoto^,1, Tsukasa Kuroki, Ryosuke Shiraishi, Takehiro Fujise, Ryuichi Iwakiri and Kazuma Fujimoto^,2

^* Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea; and Department of Internal Medicine, Saga Medical School, Saga, Saga 849-8501, Japan

To whom requests for reprints should be addressed at ² Department of Internal Medicine and Gastrointestinal Endoscopy, Saga Medical School, 5-1-1 Nabeshima, Saga, Saga 849-8501, Japan. E-mail: fujimoto{at}med.saga-u.ac.jp

Ghrelin is mainly produced in the stomach and has several physiologic functions. The aim of this study was to investigate whether ghrelin regulates apoptosis in the small intestinal mucosa of fasting rats. Intestinal mucosal apoptosis was evaluated as the percentage of fragmented DNA, villus height, and terminal deoxynucleotidyl transferase–mediated dUDP-biotin nick end-labeling (TUNEL) staining and by Western blot analysis of caspase-3 in 48-hr fasting rats. Crypt cell proliferation was evaluated by counting the number of 5-bromo-2-deoxyuridine (BrdU) positive cells. Ghrelin was administered intraperitoneally at dosages of 2.5, 25, and 250 µg/kg per 48 hrs by continuous infusion via an Alzet micro-osmotic pump or injections at 12-hr intervals. Ghrelin was also infused in rats that underwent truncal vagotomy. The lowest dosage of ghrelin (2.5 µg/kg per 48 hrs) was administered into the third cerebroventricle. Ghrelin treatment attenuated the percentage of fragmented DNA in the small intestinal mucosa in 48-hr fasting rats in a dose-dependent manner. Continuous infusion of ghrelin and injections of ghrelin at 12-hr intervals suppressed intestinal apoptosis almost equally. This effect on apoptosis was not attenuated by truncal vagotomy. Cerebroventricular infusion of ghrelin also attenuated intestinal apoptosis. The antiapoptotic effect of ghrelin was confirmed by decreased TUNEL staining, recovery of the villus height, and decreased expression of caspase-3. BrdU uptake indicated that ghrelin enhanced cell proliferation in the intestinal crypt. Taken together, these data indicate that ghrelin enhanced intestinal growth with the suppression of small intestinal mucosal apoptosis in 48-hr fasting rats, suggesting that ghrelin controls intestinal function through the regulation of intestinal apoptosis.

Key Words: small intestine • cell proliferation • intraperitoneal infusion • vagotomy

This article has been cited by other articles:

				T. Kakimoto, T. Fujise, R. Shiraishi, T. Kuroki, J. M. Park, A. Ootani, Y. Sakata, S. Tsunada, R. Iwakiri, and K. Fujimoto Indigestible Material Attenuated Changes in Apoptosis in the Fasted Rat Jejunal Mucosa Experimental Biology and Medicine, March 1, 2008; 233(3): 310 - 316. [Abstract] [Full Text] [PDF]