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

Autor: Lauren Z. Oestricker, Michael Wallendorf, Judit Dunai, Dominic N. Reeds, Burton M. Wice, C. Rachel Kilpatrick, Songyan Wang, Karin Sterl, Bruce W. Patterson
Rok vydání: 2018
Předmět:
Atropine
Blood Glucose
Male
0301 basic medicine
Peptide Hormones
medicine.medical_treatment
lcsh:Medicine
Type 2 diabetes
Biochemistry
Impaired glucose tolerance
Endocrinology
Cell Signaling
Heart Rate
Insulin Secretion
Medicine and Health Sciences
Insulin
Pancreatic polypeptide
Receptors
Cholinergic
lcsh:Science
Neurotensin
Glucose Tolerance
Cross-Over Studies
Multidisciplinary
Organic Compounds
Chemistry
Monosaccharides
Neurochemistry
Neurotransmitters
Middle Aged
Physical Sciences
Female
hormones
hormone substitutes
and hormone antagonists
Signal Transduction
Research Article
Adult
endocrine system
medicine.medical_specialty
Cholinergics
Carbohydrates
Gastric Inhibitory Polypeptide
Pancreatic Polypeptide
Glucose Signaling
Xenin
Glucagon
03 medical and health sciences
Alkaloids
Gastric inhibitory polypeptide
Internal medicine
Glucose Intolerance
medicine
Humans
Diabetic Endocrinology
Organic Chemistry
lcsh:R
Chemical Compounds
Biology and Life Sciences
Polypeptides
Cell Biology
medicine.disease
Hormones
Glucose
Metabolism
030104 developmental biology
Cholinergic
lcsh:Q
Peptides
Neuroscience
Zdroj: PLoS ONE, Vol 13, Iss 2, p e0192441 (2018)
PLoS ONE
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0192441
Popis: 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 Xen was co-administered with GIP. From 40 to 240 min, glucose levels and ISRs continually increased while glucagon concentrations declined, regardless of infusate. Atropine increased resting heart rate and blocked all PP responses but did not affect ISRs or plasma glucagon levels during any of the peptide infusions. Thus, cholinergic signaling mediates the effects of Xen on insulin and glucagon release in mice but not humans.
Databáze: OpenAIRE
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