1.Cephalic phase secretion of insulin and other enteropancreatic hormones in humans.
Veedfald S1, Plamboeck A2, Deacon CF3, Hartmann B3, Knop FK2, Vilsbøll T4, Holst JJ5. Am J Physiol Gastrointest Liver Physiol. 2016 Jan 1;310(1):G43-51. doi: 10.1152/ajpgi.00222.2015. Epub 2015 Oct 22.
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.
2.Acute load-dependent effects of oral whey protein on gastric emptying, gut hormone release, glycemia, appetite, and energy intake in healthy men.
Hutchison AT1, Piscitelli D2, Horowitz M1, Jones KL1, Clifton PM3, Standfield S1, Hausken T4, Feinle-Bisset C1, Luscombe-Marsh ND5. Am J Clin Nutr. 2015 Dec;102(6):1574-84. doi: 10.3945/ajcn.115.117556. Epub 2015 Nov 4.
BACKGROUND: In healthy individuals, intraduodenal whey protein load-dependently modulates gastrointestinal motor and hormonal functions and suppresses energy intake. The effect of oral whey, particularly the impact of load, has not been evaluated.
3.The effect of pregnane X receptor agonists on postprandial incretin hormone secretion in rats and humans.
Hukkanen J1,2,3,4, Rysa J4,5,6, Makela KA3,4,7, Herzig KH3,4,7, Hakkola J4,6, Savolainen MJ8,2,3,4. J Physiol Pharmacol. 2015 Dec;66(6):821-39.
We recently showed that pregnane X receptor (PXR) agonists cause hyperglycaemia during oral glucose tolerance test (OGTT) in rats and healthy volunteers (Rifa-1 study). We now aimed to determine if the secretion of incretin hormones, especially glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP), are affected by PXR agonists since these gut-secreted hormones are major regulators of postprandial glucose metabolism. The Rifa-2 study had a one-phase, open-label design. Twelve subjects were given 600 mg of rifampicin a day for a week. OGTT with glucose, insulin, and incretin hormone measurements was performed before and after the rifampicin dosing. Incretins and insulin were analysed in previously collected rat OGTT samples after pregnenolone 16α-carbonitrile (PCN) or control treatment for 4 days. Rifampicin treatment did not affect glucose, insulin, GLP-1, GIP, glucagon, and peptide YY levels statistically significantly.
4.Glucose-Dependent Insulinotropic Polypeptide Stimulates Osteopontin Expression in the Vasculature via Endothelin-1 and CREB.
Berglund LM1, Lyssenko V2, Ladenvall C1, Kotova O1, Edsfeldt A1, Pilgaard K3, Alkayyali S1, Brøns C3, Forsblom C4, Jonsson A1, Zetterqvist AV1, Nitulescu M1, McDavitt CR1, Dunér P1, Stancáková A5, Kuusisto J5, Ahlqvist E1, Lajer M3, Tarnow L6, Madsbad S7, Rossing P8, Kieffer TJ9, Melander O1, Orho-Melander M1, Nilsson P1, Groop PH4, Vaag A10, Lindblad B1, Gottsäter A1, Laakso M5, Goncalves I11, Groop L1, Gomez MF12. Diabetes. 2016 Jan;65(1):239-54. doi: 10.2337/db15-0122. Epub 2015 Sep 22.
Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone with extrapancreatic effects beyond glycemic control. Here we demonstrate unexpected effects of GIP signaling in the vasculature. GIP induces the expression of the proatherogenic cytokine osteopontin (OPN) in mouse arteries via local release of endothelin-1 and activation of CREB. Infusion of GIP increases plasma OPN concentrations in healthy individuals. Plasma endothelin-1 and OPN concentrations are positively correlated in patients with critical limb ischemia. Fasting GIP concentrations are higher in individuals with a history of cardiovascular disease (myocardial infarction, stroke) when compared with control subjects. GIP receptor (GIPR) and OPN mRNA levels are higher in carotid endarterectomies from patients with symptoms (stroke, transient ischemic attacks, amaurosis fugax) than in asymptomatic patients, and expression associates with parameters that are characteristic of unstable and inflammatory plaques (increased lipid accumulation, macrophage infiltration, and reduced smooth muscle cell content).
