endomorphin-2 and Diabetes-Mellitus--Type-1

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.

Topics: Animals; Colon; Diabetes Mellitus, Type 1; Gastrointestinal Transit; Male; Mice; Oligopeptides; Time Factors

To assess whether diabetes alters the regulatory effects of mu-opioid receptor (MOR) agonists on the cholinergic bronchoconstriction, we investigated the inhibitory effects of endomorphins (EMs) on the electrical field stimulation (EFS)-induced cholinergic bronchoconstriction in type 1 diabetic rats. At 4 weeks after the onset of diabetes, both the EFS- and exogenous acetylcholine (ACh)-induced bronchoconstriction in diabetes in vitro were greater than those in non-diabetes rats. Furthermore, endomorphin 1 (EM1) and endomorphin 2 (EM2) inhibited the response to EFS in diabetic rat isolated bronchus in a concentration- and frequency-dependent manner, which is in agreement with that in non-diabetes. However, the inhibitory effects of EMs on the EFS-induced bronchoconstriction in diabetes were significantly weaker than those in non-diabetes. Both EM1 and EM2 (1 microM) had no effect on the contractile response to exogenous ACh, indicating a prejunctional effect. Furthermore, the inhibitory effect on the EFS-induced bronchoconstriction was blocked by naloxone (10 microM). Eight weeks after the induction of diabetes, both the EFS- and exogenous ACh-induced bronchoconstrictions in diabetes were further enhanced compared to those in short-time (4 weeks) diabetic rats. Moreover, the inhibitory effects of EMs on the EFS-induced bronchoconstriction were further attenuated. These results suggest that dysfunction of presynaptic inhibitory modulation through opioid receptor by EMs may take place in the bronchus of diabetic rats.

Topics: Acetylcholine; Analgesics, Opioid; Animals; Bronchi; Bronchoconstriction; Diabetes Mellitus, Type 1; Electric Stimulation; Male; Oligopeptides; Rats; Rats, Wistar; Synaptic Transmission