Cholinergic signaling mediates the effects of xenin-25 on secretion of pancreatic polypeptide but not insulin or glucagon in humans with impaired glucose tolerance

PloS One
Songyan WangBurton M Wice

Abstract

We previously demonstrated that infusion of an intestinal peptide called xenin-25 (Xen) amplifies the effects of glucose-dependent insulinotropic polypeptide (GIP) on insulin secretion rates (ISRs) and plasma glucagon levels in humans. However, these effects of Xen, but not GIP, were blunted in humans with type 2 diabetes. Thus, Xen rather than GIP signaling to islets fails early during development of type 2 diabetes. The current crossover study determines if cholinergic signaling relays the effects of Xen on insulin and glucagon release in humans as in mice. Fasted subjects with impaired glucose tolerance were studied. On eight separate occasions, each person underwent a single graded glucose infusion- two each with infusion of albumin, Xen, GIP, and GIP plus Xen. Each infusate was administered ± atropine. Heart rate and plasma glucose, insulin, C-peptide, glucagon, and pancreatic polypeptide (PP) levels were measured. ISRs were calculated from C-peptide levels. All peptides profoundly increased PP responses. From 0 to 40 min, peptide(s) infusions had little effect on plasma glucose concentrations. However, GIP, but not Xen, rapidly and transiently increased ISRs and glucagon levels. Both responses were further amplified when ...Continue Reading

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Citations

Dec 29, 2019·Diabetes·Rayner Rodriguez-DiazAlejandro Caicedo
Oct 27, 2018·Frontiers in Endocrinology·Silvano Paternoster, Marco Falasca
May 20, 2020·Clinical Medicine Insights. Endocrinology and Diabetes·Andrew English, Nigel Irwin
Jul 27, 2021·Diabetes, Obesity & Metabolism·Michael A NauckAndreas F H Pfeiffer

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Methods Mentioned

BETA
blood drawn
ELISA

Clinical Trials Mentioned

NCT01951729
NCT00468091
NCT00689208
NCT00992901

Software Mentioned

SAS

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