Effects of glucagon-like peptide-1 on glucagon secretion in patients with non-alcoholic fatty liver disease
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Effects of glucagon-like peptide-1 on glucagon secretion in patients with non-alcoholic fatty liver disease. / Junker, Anders E; Gluud, Lise L; van Hall, Gerrit; Holst, Jens J; Knop, Filip K; Lauritsen, Tina Vilsbøll.
I: Journal of Hepatology, Bind 64, Nr. 4, 04.2016, s. 908–915.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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
Y1 - 2016/4
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 a 2-hour 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 calorimety.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 effects 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 normoglycaemia 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 a 2-hour 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 calorimety.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 effects 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 normoglycaemia in these patients.
U2 - 10.1016/j.jhep.2015.11.014
DO - 10.1016/j.jhep.2015.11.014
M3 - Journal article
C2 - 26626496
VL - 64
SP - 908
EP - 915
JO - Journal of Hepatology, Supplement
JF - Journal of Hepatology, Supplement
SN - 0169-5185
IS - 4
ER -
ID: 150704289