کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2005777 | 1541697 | 2016 | 9 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Metabolic responses to xenin-25 are altered in humans with Roux-en-Y gastric bypass surgery Metabolic responses to xenin-25 are altered in humans with Roux-en-Y gastric bypass surgery](/preview/png/2005777.png)
• Many effects of xenin-25 are mediated by neurotensin receptor-1 on neurons.
• Xenin increased autonomic responses in humans with and without RYGB.
• Ability of xenin to inhibit GLP-1 release and cause diarrhea was blunted after RYGB.
• Insulin and GIP secretion preceded GLP-1 release after RYGB.
• Neural circuits that regulate glucose homeostasis are altered by RYGB.
Xenin-25 (Xen) is a neurotensin-related peptide secreted by a subset of enteroendocrine cells located in the proximal small intestine. Many effects of Xen are mediated by neurotensin receptor-1 on neurons. In healthy humans with normal glucose tolerance (NGT), Xen administration causes diarrhea and inhibits postprandial glucagon-like peptide-1 (GLP‐1) release but not insulin secretion. This study determines (i) if Xen has similar effects in humans with Roux-en-Y gastric bypass (RYGB) and (ii) whether neural pathways potentially mediate effects of Xen on glucose homeostasis.Eight females with RYGB and no history of type 2 diabetes received infusions with 0, 4 or 12 pmol Xen/kg/min with liquid meals on separate occasions. Plasma glucose and gastrointestinal hormone levels were measured and insulin secretion rates calculated. Pancreatic polypeptide and neuropeptide Y levels were surrogate markers for parasympathetic input to islets and sympathetic tone, respectively. Responses were compared to those in well-matched non-surgical participants with NGT from our earlier study.Xen similarly increased pancreatic polypeptide and neuropeptide Y responses in patients with and without RYGB. In contrast, the ability of Xen to inhibit GLP-1 release and cause diarrhea was severely blunted in patients with RYGB. With RYGB, Xen had no statistically significant effect on glucose, insulin secretory, GLP-1, glucose-dependent insulinotropic peptide, and glucagon responses. However, insulin and glucose-dependent insulinotropic peptide secretion preceded GLP-1 release suggesting circulating GLP-1 does not mediate exaggerated insulin release after RYGB. Thus, Xen has unmasked neural circuits to the distal gut that inhibit GLP-1 secretion, cause diarrhea, and are altered by RYGB.
Journal: Peptides - Volume 82, August 2016, Pages 76–84