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.