title: Metabolomic profiling reveals differential effects of glucagon-like peptide-1 and insulin on nutrient partitioning in ovine liver.
abstract: This study was conducted to identify the insulin-independent actions of glucagon-like peptide-1 (GLP-1 (7-36 amide)) in partitioning nutrient metabolism in ovine liver. Four Suffolk wethers (60.0 ± 6.7 kg body weight (BW)) were used in a repeated-measure design under euglycemic--hyperinsulinemic and hyper -GLP-1 clamps for 150 min with intravenous infusion of insulin (0.5 mU/kg BW/min; from 0 to 90 min), GLP-1 (0.5 µg/kg BW/min; from 60 to 150 min) and both hormones co-administered from 60 to 90 min. Liver biopsies were collected at 0, 60, 90 and 150 min to represent the metabolomic profiling of baseline, insulin, insulin plus GLP-1, and GLP-1, respectively, and were analyzed for metabolites using Capillary Electrophoresis Time-of-Flight Mass Spectrometer. Metabolomics analysis reveals 51 metabolites as being significantly altered (P < 0.05) by insulin and GLP-1 infusion compared to baseline values. Insulin infusion enhanced glycolysis, lipogenesis, oxidative stress defense and cell proliferation pathways, but reduced protein breakdown, gluconeogenesis and ketogenesis pathways. Conversely, GLP-1 infusion promoted lipolytic and ketogenic pathways accompanied by a lowered lipid clearance from the liver as well as elevated oxidative stress defense and nucleotide degradation. Despite further research still being warranted, our data suggest that GLP-1 may exert insulin-antagonistic effects on hepatic lipid and nucleotide metabolism in ruminants.
authors.affiliation: The Research Center for Animal Science, Graduate School of Biosphere Science, Hiroshima University, Higashi Hiroshima, Japan.|Department of Nutrition and Clinical Nutrition, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafr El-Sheikh, Egypt.
authors.forename: Mabrouk
authors.initials: M
authors.lastname: El-Sabagh
authors.affiliation: The Research Center for Animal Science, Graduate School of Biosphere Science, Hiroshima University, Higashi Hiroshima, Japan.
authors.forename: Dai
authors.initials: D
authors.lastname: Taniguchi
authors.affiliation: The Research Center for Animal Science, Graduate School of Biosphere Science, Hiroshima University, Higashi Hiroshima, Japan.
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Sugino
authors.affiliation: The Research Center for Animal Science, Graduate School of Biosphere Science, Hiroshima University, Higashi Hiroshima, Japan.
authors.forename: Taketo
authors.initials: T
authors.lastname: Obitsu
mesh_terms: D000824:Animal Nutritional Physiological Phenomena / Q000235:genetics* / Q000502:physiology*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004586:Electrophoresis; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology / Q000502:physiology*; D005943:Gluconeogenesis / Q000187:drug effects; D006019:Glycolysis / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology / Q000502:physiology; D007659:Ketones / Q000378:metabolism; D050356:Lipid Metabolism; D050155:Lipogenesis / Q000187:drug effects; D008099:Liver / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D055432:Metabolomics / Q000379:methods*; D009711:Nucleotides / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D059748:Proteolysis / Q000187:drug effects; D012756:Sheep / Q000378:metabolism*
chemical_list: D007328:Insulin; D007659:Ketones; D009711:Nucleotides; D052216:Glucagon-Like Peptide 1
keywords: gut hormones; liver; metabolic functions; sheep