Neuromedin U is a gut peptide that alters oral glucose tolerance by delaying gastric emptying via direct contraction of the pylorus and vagal-dependent mechanisms.

Abstract

The gut-brain peptide neuromedin U (NMU) decreases food intake and body weight and improves glucose tolerance. Here, we characterized NMU as an enteropeptide and determined how it impacts glucose excursion. NMU was expressed predominantly in the proximal small intestine, and its secretion was triggered by ingestion of a mixed meal. Although a single peripheral injection of NMU in C57BL/6NRj mice prevented the rise of glycemia upon an oral but not an intraperitoneal load of glucose, it unexpectedly prevented insulin secretion, only slightly improved peripheral insulin sensitivity, and barely reduced intestinal glucose absorption. Interestingly, peripheral administration of NMU abrogated gastric emptying. NMU receptors 1 and 2 were detected in pyloric muscles and NMU was able to directly induce pyloric contraction in a dose-dependent manner ex vivo in isometric chambers. Using a modified glucose tolerance test, we demonstrate that improvement of oral glucose tolerance by NMU was essentially, if not exclusively, because of its impact on gastric emptying. Part of this effect was abolished in vagotomized (VagoX) mice, suggesting implication of the vagus tone. Accordingly, peripheral injection of NMU was associated with increased number of c-FOS-positive neurons in the nucleus of the solitary tract, which was partly prevented in VagoX mice. Finally, NMU kept its ability to improve oral glucose tolerance in obese and diabetic murine models. Together, these data demonstrate that NMU is an enteropeptide that prevents gastric emptying directly by triggering pylorus contraction and indirectly through vagal afferent neurons. This blockade consequently reduces intestinal nutrient absorption and thereby results in an apparent improved tolerance to oral glucose challenge.-Jarry, A.-C., Merah, N., Cisse, F., Cayetanot, F., Fiamma, M.-N., Willemetz, A., Gueddouri, D., Barka, B., Valet, P., Guilmeau, S., Bado, A., Le Beyec, J., Bodineau, L., Le Gall, M. Neuromedin U is a gut peptide that alters oral glucose tolerance by delaying gastric emptying via direct contraction of the pylorus and vagal-dependent mechanisms.

• Authors: Anne-Charlotte Jarry, Nadir Merah, Fanta Cisse, Florence Cayetanot, Marie-Noëlle Fiamma, Alexandra Willemetz, Dalale Gueddouri, Besma Barka, Philippe Valet, Sandra Guilmeau, André Bado, Johanne Le Beyec, Laurence Bodineau, Maude Le Gall
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 33 Issue 4 Pg. 5377-5388 (04 2019) ISSN: 1530-6860 [Electronic] United States
• PMID: 30753087 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Neuropeptides
• Peptides
• neuromedin U
• Glucose

Topics

• Animals
• Blood Glucose (drug effects)
• Body Weight (drug effects)
• Eating (drug effects)
• Gastric Emptying (drug effects)
• Gastrointestinal Microbiome (drug effects)
• Glucose (metabolism)
• Glucose Tolerance Test (methods)
• Male
• Mice
• Mice, Inbred C57BL
• Neuropeptides (pharmacology)
• Peptides (pharmacology)
• Pylorus (drug effects)
• Vagus Nerve (drug effects)