title: Influence of GLP-1 on myocardial glucose metabolism in healthy men during normo- or hypoglycemia.
abstract: OBJECTIVE
  Glucagon-like peptide-1 (GLP-1) may provide beneficial cardiovascular effects, possibly due to enhanced myocardial energetic efficiency by increasing myocardial glucose uptake (MGU). We assessed the effects of GLP-1 on MGU in healthy subjects during normo- and hypoglycemia.
  
  
  METHODS
  We included eighteen healthy men in two randomized, double-blinded, placebo-controlled cross-over studies. MGU was assessed with GLP-1 or saline infusion during pituitary-pancreatic normo- (plasma glucose (PG): 4.5 mM, n = 10) and hypoglycemic clamps (PG: 3.0 mM, n = 8) by positron emission tomography with (18)fluoro-deoxy-glucose ((18)F-FDG) as tracer.
  
  
  RESULTS
  In the normoglycemia study mean (± SD) age was 25±3 years, and BMI was 22.6±0.6 kg/m(2) and in the hypoglycemia study the mean age was 23±2 years with a mean body mass index of 23±2 kg/m(2). GLP-1 did not change MGU during normoglycemia (mean (+/- SD) 0.15+/-0.04 and 0.16+/-0.03 µmol/g/min, P = 0.46) or during hypoglycemia (0.16+/-0.03 and 0.13+/-0.04 µmol/g/min, P = 0.14). However, the effect of GLP-1 on MGU was negatively correlated to baseline MGU both during normo- and hypoglycemia, (P = 0.006, r(2) = 0.64 and P = 0.018, r(2) = 0.64, respectively) and changes in MGU correlated positively with the level of insulin resistance (HOMA 2IR) during hypoglycemia, P = 0.04, r(2) = 0.54. GLP-1 mediated an increase in circulating glucagon levels at PG levels below 3.5 mM and increased glucose infusion rates during the hypoglycemia study. No differences in other circulating hormones or metabolites were found.
  
  
  CONCLUSIONS
  While GLP-1 does not affect overall MGU, GLP-1 induces changes in MGU dependent on baseline MGU such that GLP-1 increases MGU in subjects with low baseline MGU and decreases MGU in subjects with high baseline MGU. GLP-1 preserves MGU during hypoglycemia in insulin resistant subjects. ClinicalTrials.gov registration numbers: NCT00418288: (hypoglycemia) and NCT00256256: (normoglycemia).
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Gejl
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: Susanne
authors.initials: S
authors.lastname: Lerche
authors.affiliation: Department of Endocrinology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Annette
authors.initials: A
authors.lastname: Mengel
authors.affiliation: Department of Endocrinology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Møller
authors.affiliation: Department of Biostatistics, Aarhus University, Aarhus, Denmark.
authors.forename: Bo Martin
authors.initials: BM
authors.lastname: Bibby
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: Kamille
authors.initials: K
authors.lastname: Smidt
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark ; Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Birgitte
authors.initials: B
authors.lastname: Brock
authors.affiliation: Department of Medicine, Viborg Regional Hospital, Viborg, Denmark.
authors.forename: Hanne
authors.initials: H
authors.lastname: Søndergaard
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Skejby, Aarhus, Denmark.
authors.forename: Hans Erik
authors.initials: HE
authors.lastname: Bøtker
authors.affiliation: PET Centre, Aarhus University Hospital, Aarhus, Denmark ; Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Albert
authors.initials: A
authors.lastname: Gjedde
authors.affiliation: Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jens Juul
authors.initials: JJ
authors.lastname: Holst
authors.affiliation: PET Centre, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Søren Baarsgaard
authors.initials: SB
authors.lastname: Hansen
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark ; Department of Endocrinology, Aarhus University Hospital, Aarhus, Denmark ; Department of Endocrinology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Jørgen
authors.initials: J
authors.lastname: Rungby
mesh_terms: D000328:Adult; D001786:Blood Glucose; D018592:Cross-Over Studies; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D006321:Heart / Q000187:drug effects*; D006728:Hormones / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000175:diagnosis / Q000378:metabolism*; D008297:Male; D055442:Metabolome; D009206:Myocardium / Q000378:metabolism*; D049268:Positron-Emission Tomography; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D006728:Hormones; D019788:Fluorodeoxyglucose F18; D052216:Glucagon-Like Peptide 1; D005947:Glucose