Xenin-25 delays gastric emptying and reduces postprandial glucose levels in humans with and without Type 2 diabetes
| العنوان: | Xenin-25 delays gastric emptying and reduces postprandial glucose levels in humans with and without Type 2 diabetes |
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| المؤلفون: | Judit Dunai, Hung D. Tran, Sara Chowdhury, Bruce W. Patterson, Songyan Wang, Burton M. Wice, Erin Laciny, Michael Wallendorf, Dan L. Crimmins, David A. Rometo, Kenneth S. Polonsky, Terry A. Griest, Dominic N. Reeds, Jack H. Ladenson |
| المصدر: | American Journal of Physiology-Gastrointestinal and Liver Physiology. 306:G301-G309 |
| بيانات النشر: | American Physiological Society, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Adult, Blood Glucose, Male, medicine.medical_specialty, Time Factors, Physiology, medicine.medical_treatment, Incretin, Enteroendocrine cell, Xenin, Glucagon, Drug Administration Schedule, Neuroregulation and Motility, Glucagon-Like Peptide 1, Physiology (medical), Internal medicine, Humans, Hypoglycemic Agents, Insulin, Receptors, Neurotensin, Medicine, Infusions, Intravenous, Neurotensin, Cross-Over Studies, Missouri, C-Peptide, Hepatology, Gastric emptying, business.industry, digestive, oral, and skin physiology, Gastroenterology, Middle Aged, Postprandial Period, Glucagon-like peptide-1, Treatment Outcome, Endocrinology, Postprandial, Diabetes Mellitus, Type 2, Gastric Emptying, Female, business, hormones, hormone substitutes, and hormone antagonists, Biomarkers |
| الوصف: | Xenin-25 (Xen) is a neurotensin-related peptide secreted by a subset of glucose-dependent insulinotropic polypeptide (GIP)-producing enteroendocrine cells. In animals, Xen regulates gastrointestinal function and glucose homeostasis, typically by initiating neural relays. However, little is known about Xen action in humans. This study determines whether exogenously administered Xen modulates gastric emptying and/or insulin secretion rates (ISRs) following meal ingestion. Fasted subjects with normal (NGT) or impaired (IGT) glucose tolerance and Type 2 diabetes mellitus (T2DM; n = 10–14 per group) ingested a liquid mixed meal plus acetaminophen (ACM; to assess gastric emptying) at time zero. On separate occasions, a primed-constant intravenous infusion of vehicle or Xen at 4 (Lo-Xen) or 12 (Hi-Xen) pmol·kg−1·min−1was administered from zero until 300 min. Some subjects with NGT received 30- and 90-min Hi-Xen infusions. Plasma ACM, glucose, insulin, C-peptide, glucagon, Xen, GIP, and glucagon-like peptide-1 (GLP-1) levels were measured and ISRs calculated. Areas under the curves were compared for treatment effects. Infusion with Hi-Xen, but not Lo-Xen, similarly delayed gastric emptying and reduced postprandial glucose levels in all groups. Infusions for 90 or 300 min, but not 30 min, were equally effective. Hi-Xen reduced plasma GLP-1, but not GIP, levels without altering the insulin secretory response to glucose. Intense staining for Xen receptors was detected on PGP9.5-positive nerve fibers in the longitudinal muscle of the human stomach. Thus Xen reduces gastric emptying in humans with and without T2DM, probably via a neural relay. Moreover, endogenous GLP-1 may not be a major enhancer of insulin secretion in healthy humans under physiological conditions. |
| تدمد: | 1522-1547 0193-1857 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4334693038f01ee022c6739e64f88e95Test https://doi.org/10.1152/ajpgi.00383.2013Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4334693038f01ee022c6739e64f88e95 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15221547 01931857 |
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