title: Direct effect of incretin hormones on glucose and glycerol metabolism and hemodynamics.
abstract: The objective of this study was to assess the insulin-independent effects of incretin hormones on glucose and glycerol metabolism and hemodynamics under euglycemic and hyperglycemic conditions. Young, healthy men (n=10) underwent three trials in a randomized, controlled, crossover study. Each trial consisted of a two-stage (euglycemia and hyperglycemia) pancreatic clamp (using somatostatin to prevent endogenous insulin secretion). Glucose and lipid metabolism was measured via infusion of stable glucose and glycerol isotopic tracers. Hemodynamic variables (femoral, brachial, and common carotid artery blood flow and flow-mediated dilation of the brachial artery) were also measured. The three trials differed as follows: 1) saline [control (CON)], 2) glucagon-like peptide (GLP-1, 0.5 pmol·kg(-1)·min(-1)), and 3) glucose-dependent insulinotropic polypeptide (GIP, 1.5 pmol·kg(-1)·min(-1)). No between-trial differences in glucose infusion rates (GIR) or glucose or glycerol kinetics were seen during euglycemia, whereas hyperglycemia resulted in increased GIR and glucose rate of disappearance during GLP-1 compared with CON and GIP (P<0.01 for all). However, when normalized to insulin levels, no differences between trials were seen for GIR or glucose rate of disappearance. Besides a higher femoral blood flow during hyperglycemia with GIP (vs. CON and GLP-1, P<0.001), no between-trial differences were seen for the hemodynamic variables. In conclusion, GLP-1 and GIP have no direct effect on whole body glucose metabolism or hemodynamics during euglycemia. On the contrary, during hyperglycemia, GIP increases femoral artery blood flow with no effect on glucose metabolism, whereas GLP-1 increases glucose disposal, potentially due to increased insulin levels.
authors.affiliation: Centre of Inflammation and Metabolism and Centre for Physical Activity Research, Department of Infectious Diseases, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Kristian
authors.initials: K
authors.lastname: Karstoft
authors.affiliation: Centre of Inflammation and Metabolism and Centre for Physical Activity Research, Department of Infectious Diseases, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; University of Southern Denmark, Odense, Denmark; and.
authors.forename: Stefan P
authors.initials: SP
authors.lastname: Mortensen
authors.affiliation: Centre of Inflammation and Metabolism and Centre for Physical Activity Research, Department of Infectious Diseases, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Sine H
authors.initials: SH
authors.lastname: Knudsen
authors.affiliation: Centre of Inflammation and Metabolism and Centre for Physical Activity Research, Department of Infectious Diseases, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Biomedical Sciences, Panum Institute, University of Copenhagen, Copenhagen, Denmark thomas.solomon@sund.ku.dk.
authors.forename: Thomas P J
authors.initials: TP
authors.lastname: Solomon
mesh_terms: D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D017536:Carotid Artery, Common / Q000187:drug effects / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D005990:Glycerol / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D054795:Incretins / Q000494:pharmacology*; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D012039:Regional Blood Flow / Q000187:drug effects; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D054795:Incretins; D005947:Glucose; D005990:Glycerol
keywords: glucagon-like peptide-1; glucose disposal; glucose effectiveness; glucose kinetics; glucose-dependent insulinotropic polypeptide; hemodynamics; hyperglycemia; pancreatic clamp; somatostatin