Effects of glucagon-like peptide-1 on glucagon secretion in patients with non-alcoholic fatty liver disease

TY - JOUR

T1 - Effects of glucagon-like peptide-1 on glucagon secretion in patients with non-alcoholic fatty liver disease

AU - Junker, Anders E

AU - Gluud, Lise L

AU - van Hall, Gerrit

AU - Holst, Jens J

AU - Knop, Filip K

AU - Lauritsen, Tina Vilsbøll

N1 - Copyright © 2015. Published by Elsevier B.V.

PY - 2016/4/1

Y1 - 2016/4/1

N2 - Background & Aims We evaluated the glucagon-suppressive effect of glucagon-like peptide-1 (GLP-1) and its potential effects on endogenous glucose production and whole body lipolysis in non-diabetic patients with non-alcoholic fatty liver disease (NAFLD). Methods On two separate days, 10 non-diabetic patients with liver biopsy-verified NAFLD (NAFLD activity score 2.5 ± 1.0) and 10 matched controls underwent 2 h intravenous infusions of GLP-1 (0.8 pmol × kg-1 × min-1) and placebo. Since GLP-1-mediated glucagon suppression has been shown to be glucose-dependent, plasma glucose was clamped at fasting level during the first hour, and then raised and clamped at 'postprandial level' (fasting plasma glucose level plus 3 mmol/L) for the remaining hour. We evaluated relative plasma levels of glucagon, endogenous glucose production and whole body lipolysis rates with stable isotopes and respiratory quotient using indirect calorimetry. Results Compared to controls, patients with NAFLD were insulin resistant (homeostasis model assessment (HOMAIR): 3.8 ± 2.2 vs. 1.6 ± 1.5, p = 0.003) and had fasting hyperglucagonaemia (7.5 ± 5.3 vs. 5.8 ± 1.5 mmol/L, p = 0.045). Similar relative glucagon suppression was seen in both groups during GLP-1 infusion at fasting (-97 ± 75 vs. -93 ± 41 pmol/L × min-1 p = 0.566) and 'postprandial' plasma glucose levels (-108 ± 101 vs. -97 ± 53 pmol/L × min-1, p = 0.196). Increased insulinotropic effect of GLP-1 was observed in NAFLD patients. No effect of GLP-1 on endogenous glucose production was observed in any of the groups. Conclusions Patients with NAFLD exhibited fasting hyperglucagonaemia, but intact GLP-1-mediated glucagon suppression independently of plasma glucose concentrations. Preserved glucagonostatic effect and increased insulinotropic effects of GLP-1 in NAFLD may be important to maintain normo-glycaemia in these patients.

AB - Background & Aims We evaluated the glucagon-suppressive effect of glucagon-like peptide-1 (GLP-1) and its potential effects on endogenous glucose production and whole body lipolysis in non-diabetic patients with non-alcoholic fatty liver disease (NAFLD). Methods On two separate days, 10 non-diabetic patients with liver biopsy-verified NAFLD (NAFLD activity score 2.5 ± 1.0) and 10 matched controls underwent 2 h intravenous infusions of GLP-1 (0.8 pmol × kg-1 × min-1) and placebo. Since GLP-1-mediated glucagon suppression has been shown to be glucose-dependent, plasma glucose was clamped at fasting level during the first hour, and then raised and clamped at 'postprandial level' (fasting plasma glucose level plus 3 mmol/L) for the remaining hour. We evaluated relative plasma levels of glucagon, endogenous glucose production and whole body lipolysis rates with stable isotopes and respiratory quotient using indirect calorimetry. Results Compared to controls, patients with NAFLD were insulin resistant (homeostasis model assessment (HOMAIR): 3.8 ± 2.2 vs. 1.6 ± 1.5, p = 0.003) and had fasting hyperglucagonaemia (7.5 ± 5.3 vs. 5.8 ± 1.5 mmol/L, p = 0.045). Similar relative glucagon suppression was seen in both groups during GLP-1 infusion at fasting (-97 ± 75 vs. -93 ± 41 pmol/L × min-1 p = 0.566) and 'postprandial' plasma glucose levels (-108 ± 101 vs. -97 ± 53 pmol/L × min-1, p = 0.196). Increased insulinotropic effect of GLP-1 was observed in NAFLD patients. No effect of GLP-1 on endogenous glucose production was observed in any of the groups. Conclusions Patients with NAFLD exhibited fasting hyperglucagonaemia, but intact GLP-1-mediated glucagon suppression independently of plasma glucose concentrations. Preserved glucagonostatic effect and increased insulinotropic effects of GLP-1 in NAFLD may be important to maintain normo-glycaemia in these patients.

U2 - 10.1016/j.jhep.2015.11.014

DO - 10.1016/j.jhep.2015.11.014

M3 - Journal article

C2 - 26626496

SN - 0168-8278

VL - 64

SP - 908

EP - 915

JO - Journal of Hepatology

JF - Journal of Hepatology

IS - 4

ER -