Characterization of oral and intravenous glucose handling in truncally vagotomised subjects with pyloroplasty

TY - JOUR

T1 - Characterization of oral and intravenous glucose handling in truncally vagotomised subjects with pyloroplasty

AU - Plamboeck, Astrid

AU - Veedfald, Simon

AU - Deacon, Carolyn

AU - Hartmann, Bolette

AU - Wettergren, Andre

AU - Svendsen, Lars Bo

AU - Meisner, Søren

AU - Hovendal, Claus

AU - Knop, Filip Krag

AU - Vilsbøll, Tina

AU - Holst, Jens Juul

PY - 2013/8

Y1 - 2013/8

N2 - Objective: Glucagon-like peptide 1 (GLP1) is rapidly inactivated by dipeptidyl peptidase 4 (DPP4), but may interact with vagal neurons at its site of secretion. We investigated the role of vagal innervation for handling of oral and i.v. glucose. Design and methods: Truncally vagotomised subjects (nZ16) and matched controls (nZ10) underwent 50 g-oral glucose tolerance test (OGTT)Gvildagliptin, a DPP4 inhibitor (DPP4i) and isoglycaemic i.v. glucose infusion (IIGI), copying the OGTT without DPP4i. Results: Isoglycaemia was obtained with 25G2 g glucose in vagotomised subjects and 18G2 g in controls (P!0.03); thus, gastrointestinal-mediated glucose disposal (GIGD) - a measure of glucose handling (100%×(glucoseOGTT-glucoseIIGI/ glucoseOGTT)) - was reduced in the vagotomised compared with the control group. Peak intact GLP1 concentrations were higher in the vagotomised group. Gastric emptying was faster in vagotomised subjects after OGTT and was unaffected by DPP4i. The early glucose-dependent insulinotropic polypeptide response was higher in vagotomised subjects. Despite this, the incretin effect was equal in both groups. DPP4i enhanced insulin secretion in controls, but had no effect in the vagotomised subjects. Controls suppressed glucagon concentrations similarly, irrespective of the route of glucose administration, whereas vagotomised subjects showed suppression only during IIGI and exhibited hyperglucagonaemia following OGTT. DPP4i further suppressed glucagon secretion in controls and tended to normalise glucagon responses in vagotomised subjects. Conclusions: GIGD is diminished, but the incretin effect is unaffected in vagotomised subjects despite higher GLP1 levels. This, together with the small effect of DPP4i, is compatible with the notion that part of the physiological effects of GLP1 involves vagal transmission.

AB - Objective: Glucagon-like peptide 1 (GLP1) is rapidly inactivated by dipeptidyl peptidase 4 (DPP4), but may interact with vagal neurons at its site of secretion. We investigated the role of vagal innervation for handling of oral and i.v. glucose. Design and methods: Truncally vagotomised subjects (nZ16) and matched controls (nZ10) underwent 50 g-oral glucose tolerance test (OGTT)Gvildagliptin, a DPP4 inhibitor (DPP4i) and isoglycaemic i.v. glucose infusion (IIGI), copying the OGTT without DPP4i. Results: Isoglycaemia was obtained with 25G2 g glucose in vagotomised subjects and 18G2 g in controls (P!0.03); thus, gastrointestinal-mediated glucose disposal (GIGD) - a measure of glucose handling (100%×(glucoseOGTT-glucoseIIGI/ glucoseOGTT)) - was reduced in the vagotomised compared with the control group. Peak intact GLP1 concentrations were higher in the vagotomised group. Gastric emptying was faster in vagotomised subjects after OGTT and was unaffected by DPP4i. The early glucose-dependent insulinotropic polypeptide response was higher in vagotomised subjects. Despite this, the incretin effect was equal in both groups. DPP4i enhanced insulin secretion in controls, but had no effect in the vagotomised subjects. Controls suppressed glucagon concentrations similarly, irrespective of the route of glucose administration, whereas vagotomised subjects showed suppression only during IIGI and exhibited hyperglucagonaemia following OGTT. DPP4i further suppressed glucagon secretion in controls and tended to normalise glucagon responses in vagotomised subjects. Conclusions: GIGD is diminished, but the incretin effect is unaffected in vagotomised subjects despite higher GLP1 levels. This, together with the small effect of DPP4i, is compatible with the notion that part of the physiological effects of GLP1 involves vagal transmission.

U2 - 10.1530/EJE-13-0264

DO - 10.1530/EJE-13-0264

M3 - Journal article

C2 - 23704713

SN - 0804-4643

VL - 169

SP - 187

EP - 201

JO - European Journal of Endocrinology

JF - European Journal of Endocrinology

ER -