Evidence that central pathways that mediate defecation utilize ghrelin receptors but do not require endogenous ghrelin

In laboratory animals and in human, centrally penetrant ghrelin receptor agonists, given systemically or orally, cause defecation. Animal studies show that the effect is due to activation of ghrelin receptors in the spinal lumbosacral defecation centers. However, it is not known whether there is a physiological role of ghrelin or the ghrelin receptor in the control of defecation. Using immunohistochemistry and immunoassay, we detected and measured ghrelin in the stomach, but were unable to detect ghrelin by either method in the lumbosacral spinal cord, or other regions of the CNS In rats in which the thoracic spinal cord was transected 5 weeks before, the effects of a ghrelin agonist on colorectal propulsion were significantly enhanced, but defecation caused by water avoidance stress (WAS) was reduced. In knockout rats that expressed no ghrelin and in wild-type rats, WAS-induced defecation was reduced by a ghrelin receptor antagonist, to similar extents. We conclude that the ghrelin receptors of the lumbosacral defecation centers have a physiological role in the control of defecation, but that their role is not dependent on ghrelin. This implies that a transmitter other than ghrelin engages the ghrelin receptor or a ghrelin receptor complex

Effects of chromium supplementation on physiology, feed intake, and insulin related metabolism in growing pigs subjected to heat stress

Improving insulin sensitivity may reduce impacts of heat stress (HS) in pigs by facilitating heat dissipation. Chromium (Cr) has been reported to improve insulin sensitivity in pigs. Therefore, the aim of this experiment was to investigate whether Cr supplementation can mitigate HS in growing pigs. Thirty-six gilts were randomly assigned to 2 diets containing 0 (control) or 400 ppb Cr. After 14 d the supplemented pigs were allocated to either 8 d thermoneutral (20°C constant; TN) or cyclic HS (35°C, 0900 h to 1700 h) conditions and continued their respective diet (n = 9 per group). Growth performance was recorded during the 14-d supplementation period. The physiological responses to HS were monitored by measuring respiration rate, rectal temperature, blood gas chemistry, and feed intake during thermal exposure. Kinetics of plasma glucose, insulin and NEFA were studied by intravenous glucose tolerance test (IVGTT) on d 8 of thermal treatment. Results showed Cr alleviated the HS-increased rectal temperature (P < 0.05) and respiration rate (P < 0.01) at 1300 h and 1600 h during thermal exposure. However, Cr did not mitigate the reduction in average daily feed intake which was reduced by 35% during HS or the HS-induced respiratory alkalosis. Chromium tended to increase average daily gain (0.86 vs. 0.95 kg, P = 0.070) during the 14-d supplementation under TN conditions before thermal exposure, which might be associated with the potential of Cr in improving overall insulin sensitivity, as evidenced by a reduced insulin resistance index calculated by Homeostatic Model Assessment (HOMA-IR; 0.65 vs. 0.51, P = 0.013) and a tendency of reduced fasting plasma insulin concentration (1.97 vs. 1.67 μU/mL, P = 0.094). Heat stress decreased the acute insulin releasing rate (P = 0.012) and consequently slowed glucose clearance rate (P = 0.035) during IVGTT. Besides, HS enlarged the values of area under the curve of NEFA during IVGTT (P < 0.01), indicating a reduced lipid mobilization. In conclusion, HS reduced insulin response to IVGTT. Chromium supplementation exhibited a potential in improving insulin sensitivity and mitigating HS symptoms in growing pigs

Ghrelin and motilin receptors as drug targets for gastrointestinal disorders

G.J.S. is currently in receipt of a student CASE award from the British Biotechnology Science Research Council, sponsored by GlaxoSmithKline, and receives research funding from Takeda Pharmaceuticals