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Am J Physiol Gastrointest Liver Physiol. 2016 Jan 1;310(1):G43-51. doi: 10.1152/ajpgi.00222.2015. Epub 2015 Oct 22.

Cephalic phase secretion of insulin and other enteropancreatic hormones in humans.

Author information

1
Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark; Department of Biomedical Sciences, The Panum Institute, University of Copenhagen, Copenhagen, Denmark; NNF Center for Basic Metabolic Research, The Panum Institute, University of Copenhagen, Copenhagen, Denmark; and Department of Surgical Gastroenterology, Rigshospitalet, University of Copenhagen, Denmark.
2
Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark; Department of Biomedical Sciences, The Panum Institute, University of Copenhagen, Copenhagen, Denmark; NNF Center for Basic Metabolic Research, The Panum Institute, University of Copenhagen, Copenhagen, Denmark; and.
3
Department of Biomedical Sciences, The Panum Institute, University of Copenhagen, Copenhagen, Denmark; NNF Center for Basic Metabolic Research, The Panum Institute, University of Copenhagen, Copenhagen, Denmark; and.
4
Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark;
5
Department of Biomedical Sciences, The Panum Institute, University of Copenhagen, Copenhagen, Denmark; NNF Center for Basic Metabolic Research, The Panum Institute, University of Copenhagen, Copenhagen, Denmark; and jjholst@sund.ku.dk.

Abstract

Enteropancreatic hormone secretion is thought to include a cephalic phase, but the evidence in humans is ambiguous. We studied vagally induced gut hormone responses with and without muscarinic blockade in 10 glucose-clamped healthy men (age: 24.5 ± 0.6 yr, means ± SE; body mass index: 24.0 ± 0.5 kg/m(2); HbA1c: 5.1 ± 0.1%/31.4 ± 0.5 mmol/mol). Cephalic activation was elicited by modified sham feeding (MSF, aka "chew and spit") with or without atropine (1 mg bolus 45 min before MSF + 80 ng·kg(-1)·min(-1) for 2 h). To mimic incipient prandial glucose excursions, glucose levels were clamped at 6 mmol/l on all days. The meal stimulus for the MSF consisted of an appetizing breakfast. Participants (9/10) also had a 6 mmol/l glucose clamp without MSF. Pancreatic polypeptide (PP) levels rose from 6.3 ± 1.1 to 19.9 ± 6.8 pmol/l (means ± SE) in response to MSF and atropine lowered basal PP levels and abolished the MSF response. Neither insulin, C-peptide, glucose-dependent insulinotropic polypeptide (GIP), nor glucagon-like peptide-1 (GLP-1) levels changed in response to MSF or atropine. Glucagon and ghrelin levels were markedly attenuated by atropine prior to and during the clamp: at t = 105 min on the atropine (ATR) + clamp (CLA) + MSF compared with the saline (SAL) + CLA and SAL + CLA + MSF days; baseline-subtracted glucagon levels were -10.7 ± 1.1 vs. -4.0 ± 1.1 and -4.7 ± 1.9 pmol/l (means ± SE), P < 0.0001, respectively; corresponding baseline-subtracted ghrelin levels were 303 ± 36 vs. 39 ± 38 and 3.7 ± 21 pg/ml (means ± SE), P < 0.0001. Glucagon and ghrelin levels were unaffected by MSF. Despite adequate PP responses, a cephalic phase response was absent for insulin, glucagon, GLP-1, GIP, and ghrelin.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01534442.

KEYWORDS:

atropine; cephalic phase; efferent vagal signaling; ghrelin; glucagon; hyperglycemic clamp insulin; muscarinic blockade; pancreatic polypeptide; vagus

PMID:
26492921
DOI:
10.1152/ajpgi.00222.2015
[Indexed for MEDLINE]
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