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Metabolomic profiling reveals differential effects of glucagon‐like peptide‐1 and insulin on nutrient partitioning in ovine liver
Author(s) -
ElSabagh Mabrouk,
Taniguchi Dai,
Sugino Toshihisa,
Obitsu Taketo
Publication year - 2016
Publication title -
animal science journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.606
H-Index - 38
eISSN - 1740-0929
pISSN - 1344-3941
DOI - 10.1111/asj.12614
Subject(s) - insulin , medicine , gluconeogenesis , endocrinology , ketogenesis , glucagon , glucagon like peptide 1 , metabolomics , lipogenesis , chemistry , lipolysis , lipid metabolism , metabolome , glycolysis , metabolism , biology , ketone bodies , diabetes mellitus , metabolite , adipose tissue , type 2 diabetes , bioinformatics
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.