Document Detail


The combination of GIP plus xenin-25 indirectly increases pancreatic polypeptide release in humans with and without type 2 diabetes mellitus.
MedLine Citation:
PMID:  24183983     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Xenin-25 (Xen) is a 25-amino acid neurotensin-related peptide that activates neurotensin receptor-1 (NTSR1). We previously showed that Xen increases the effect of glucose-dependent insulinotropic polypeptide (GIP) on insulin release 1) in hyperglycemic mice via a cholinergic relay in the periphery independent from the central nervous system and 2) in humans with normal or impaired glucose tolerance, but not type 2 diabetes mellitus (T2DM). Since this blunted response to Xen defines a novel defect in T2DM, it is important to understand how Xen regulates islet physiology. On separate visits, subjects received intravenous graded glucose infusions with vehicle, GIP, Xen, or GIP plus Xen. The pancreatic polypeptide response was used as an indirect measure of cholinergic input to islets. The graded glucose infusion itself had little effect on the pancreatic polypeptide response whereas administration of Xen equally increased the pancreatic polypeptide response in humans with normal glucose tolerance, impaired glucose tolerance, and T2DM. The pancreatic polypeptide response to Xen was similarly amplified by GIP in all 3 groups. Antibody staining of human pancreas showed that NTSR1 is not detectable on islet endocrine cells, sympathetic neurons, blood vessels, or endothelial cells but is expressed at high levels on PGP9.5-positive axons in the exocrine tissue and at low levels on ductal epithelial cells. PGP9.5 positive nerve fibers contacting beta cells in the islet periphery were also observed. Thus, a neural relay, potentially involving muscarinic acetylcholine receptors, indirectly increases the effects of Xen on pancreatic polypeptide release in humans.
Authors:
Sara Chowdhury; Songyan Wang; Bruce W Patterson; Dominic N Reeds; Burton M Wice
Related Documents :
23891763 - Long-term liraglutide treatment is associated with increased insulin content and secret...
24720683 - Effect of hyperglycaemia on muscarinic m3 receptor expression and secretory sensitivity...
22901243 - Plasma ykl-40 predicts 10-year cardiovascular and all-cause mortality in individuals wi...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-10-29
Journal Detail:
Title:  Regulatory peptides     Volume:  187     ISSN:  1873-1686     ISO Abbreviation:  Regul. Pept.     Publication Date:  2013 Nov 
Date Detail:
Created Date:  2013-11-27     Completed Date:  2014-07-16     Revised Date:  2014-11-12    
Medline Journal Info:
Nlm Unique ID:  8100479     Medline TA:  Regul Pept     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  42-50     Citation Subset:  IM    
Copyright Information:
© 2013.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Adult
Blood Glucose
Case-Control Studies
Cholinergic Neurons / drug effects,  metabolism
Diabetes Mellitus, Type 2 / blood*
Female
Gastric Inhibitory Polypeptide / pharmacology*
Humans
Male
Middle Aged
Neurotensin / pharmacology*
Pancreas / drug effects,  innervation*,  secretion
Pancreatic Polypeptide / blood,  secretion*
Pancreatic Polypeptide-Secreting Cells / metabolism
Receptors, Neurotensin / metabolism
Grant Support
ID/Acronym/Agency:
5R01 DK008126/DK/NIDDK NIH HHS; 5RC1 DK086163/DK/NIDDK NIH HHS; P30 CA91842/CA/NCI NIH HHS; P30 DK020579/DK/NIDDK NIH HHS; P30 DK056341/DK/NIDDK NIH HHS; P30 DK056341/DK/NIDDK NIH HHS; P30 DK52574-16/DK/NIDDK NIH HHS; P41 RR000954/RR/NCRR NIH HHS; P41 RR00954/RR/NCRR NIH HHS; P60 DK020579/DK/NIDDK NIH HHS; P60 DK020579/DK/NIDDK NIH HHS; R01 DK088126/DK/NIDDK NIH HHS; RC1 DK086163/DK/NIDDK NIH HHS; UL1 RR024992/RR/NCRR NIH HHS; UL1 RR024992/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Blood Glucose; 0/Receptors, Neurotensin; 0/neurotensin type 1 receptor; 144092-28-4/xenin 25; 39379-15-2/Neurotensin; 59392-49-3/Gastric Inhibitory Polypeptide; 59763-91-6/Pancreatic Polypeptide
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  GC-MS determination of bisphenol A and alkylphenol ethoxylates in river water from India and their e...
Next Document:  Central administration of mesotocin inhibits feeding behavior in chicks.