Cephalic phase secretion of insulin and other enteropancreatic hormones in humans.
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.
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.
Simon
S
Veedfald
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.
Astrid
A
Plamboeck
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.
Carolyn F
CF
Deacon
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.
Bolette
B
Hartmann
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.
Filip K
FK
Knop
Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark;
Tina
T
Vilsbøll
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.
Jens J
JJ
Holst
D000328:Adult; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D003718:Denmark; D004435:Eating; D005749:Gastric Inhibitory Polypeptide / Q000097:blood / Q000378:metabolism; D054439:Ghrelin / Q000097:blood / Q000378:metabolism; D005934:Glucagon / Q000097:blood / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000097:blood / Q000378:metabolism; D015309:Glucose Clamp Technique; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007413:Intestinal Mucosa / Q000378:metabolism; D007419:Intestinal Secretions / Q000378:metabolism*; D007422:Intestines / Q000294:innervation*; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010179:Pancreas / Q000378:metabolism*; D010191:Pancreatic Polypeptide / Q000097:blood / Q000378:metabolism; D019518:Postprandial Period; D013997:Time Factors; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*; D055815:Young Adult
D015415:Biomarkers; D001786:Blood Glucose; C515349:GHRL protein, human; D054439:Ghrelin; D007328:Insulin; D018727:Muscarinic Antagonists; D005749:Gastric Inhibitory Polypeptide; D010191:Pancreatic Polypeptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon
atropine; cephalic phase; efferent vagal signaling; ghrelin; glucagon; hyperglycemic clamp insulin; muscarinic blockade; pancreatic polypeptide; vagus