title: In vivo characterization of intestinal effects of endomorphin-1 and endomorphin-2 in type 1 diabetic mice.
abstract: Previously, we have demonstrated that type 1 diabetes significantly attenuated the effects of endomorphins on mouse colonic contractions in vitro. In the present study, to further assess whether diabetes affects the in vivo effects of endomorphins on the mouse intestinal motility, we investigated the effects of endomorphins on colonic propulsion and large intestinal transit in diabetic mice. Both colonic bead expulsion and large intestinal transit were significantly delayed in 4 and 8 weeks diabetic mice compared to non-diabetic mice. Moreover, intracerebroventricular (i.c.v.) administration of EM-1 and EM-2 (0.5, 1.5 and 5 nmol/mouse) significantly increased bead expulsion latency in a dose-dependent manner both in non-diabetic and diabetic mice. Similar results were found in large intestinal transit. However, the inhibitory effects of colonic propulsion induced by endomorphins were significantly attenuated in diabetes compared to non-diabetes. It is noteworthy that the inhibition of distal colonic propulsion induced by EM-1 in 8-week diabetes was lower than that of in 4 weeks diabetes. Nevertheless, there was no significant influence on endomorphins-induced inhibition of large intestinal transit caused by diabetes. Co-administration of naloxone (10 nmol/mouse, i.c.v.) significantly attenuated the inhibitory effects of endomorphins (5 nmol/mouse, i.c.v.) on colonic bead expulsion and large intestinal transit in 4 weeks diabetes, indicating that opioid receptor involved in these effects. Our results indicated that type 1 diabetes attenuated the inhibition of distal colonic propulsion induced by endomorphins in mice, but not the large intestine. The central opioid mechanism was involved in the endomorphins-induced intestinal effects in diabetes.
authors.affiliation: School of Life Science and Technology, Harbin Institute of Technology, 92 West Dazhi Street, Harbin 150001, China. wangcl@hit.edu.cn
authors.forename: Chang-Lin
authors.initials: CL
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.forename: Chao
authors.initials: C
authors.lastname: Guo
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
mesh_terms: D000818:Animals; D003106:Colon / Q000187:drug effects* / Q000503:physiopathology*; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D005772:Gastrointestinal Transit / Q000187:drug effects; D008297:Male; D051379:Mice; D009842:Oligopeptides / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D009842:Oligopeptides; C105293:endomorphin 1; C105294:endomorphin 2