スエヨシ　リヨウ   末吉　亮    所属   医学部 医学科（東京女子医科大学病院）    職種   講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Stimulation of intestinal growth and function with DPP4 inhibition in a mouse short bowel syndrome model.
掲載誌名	正式名：American journal of physiology. Gastrointestinal and liver physiology 略　 称：Am J Physiol Gastrointest Liver Physiol ISSNコード：15221547/01931857
掲載区分	国外
巻・号・頁	307(4),pp.G410-419
著者・共著者	Sueyoshi Ryo†, Woods Ignatoski Kathleen M, Okawada Manabu, Hartmann Bolette, Holst Jens, Teitelbaum Daniel H
担当区分	筆頭著者
発行年月	2014/08
概要	Glucagon-like peptide-2 (GLP-2) has been shown to be effective in patients with short bowel syndrome (SBS), but it is rapidly inactivated by dipeptidyl peptidase IV (DPP4). We used an orally active DPP4 inhibitor (DPP4-I), MK-0626, to determine the efficacy of this approach to promote adaptation after SBS, determined optimal dosing, and identified further functional actions in a mouse model of SBS. Ten-week-old mice underwent a 50% proximal small bowel resection. Dose optimization was determined over a 3-day post-small bowel resection period. The established optimal dose was given for 7, 30, and 90 days and for 7 days followed by a 23-day washout period. Adaptive response was assessed by morphology, intestinal epithelial cell (IEC) proliferation (proliferating cell nuclear antigen), epithelial barrier function (transepithelial resistance), RT-PCR for intestinal transport proteins and GLP-2 receptor, IGF type 1 receptor, and GLP-2 plasma levels. Glucose-stimulated sodium transport was assessed for intestinal absorptive function. Seven days of DPP4-I treatment facilitated an increase in GLP-2 receptor levels, intestinal growth, and IEC proliferation. Treatment led to differential effects over time, with greater absorptive function at early time points and enhanced proliferation at later time points. Interestingly, adaptation continued in the group treated for 7 days followed by a 23-day washout. DPP4-I enhanced IEC proliferative action up to 90 days postresection, but this action seemed to peak by 30 days, as did GLP-2 plasma levels. Thus DPP4-I treatment may prove to be a viable option for accelerating intestinal adaptation with SBS.
DOI	10.1152/ajpgi.00363.2013
PMID	24970775