title: Effects of glucagon-like peptide-1 on glucagon secretion in patients with non-alcoholic fatty liver disease.
abstract: OBJECTIVE
  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 2h 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 (HOMA(IR)): 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.
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark; NNF Centre for Basic Metabolic Research and Department of Biomedical Science, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Anders E
authors.initials: AE
authors.lastname: Junker
authors.affiliation: Department of Gastroenterology, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark.
authors.forename: Lise L
authors.initials: LL
authors.lastname: Gluud
authors.affiliation: Clinical Metabolomics Core Facility, Rigshospitalet, University of Copenhagen, Denmark.
authors.forename: Gerrit
authors.initials: G
authors.lastname: van Hall
authors.affiliation: NNF Centre for Basic Metabolic Research and Department of Biomedical Science, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark; NNF Centre for Basic Metabolic Research and Department of Biomedical Science, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Filip K
authors.initials: FK
authors.lastname: Knop
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark. Electronic address: t.vilsboll@dadlnet.dk.
authors.forename: Tina
authors.initials: T
authors.lastname: Vilsbøll
mesh_terms: D000328:Adult; D000368:Aged; D004734:Energy Metabolism; D005260:Female; D005934:Glucagon / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology*; D005947:Glucose / Q000096:biosynthesis; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D008066:Lipolysis; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000378:metabolism*
chemical_list: D007328:Insulin; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D005947:Glucose
keywords: Endogenous glucose production; Energy metabolism; Glucagon; Glucagon-like peptide-1 (GLP-1); Lipolysis; Non-alcoholic fatty liver disease (NAFLD)