Metabolomic profiling reveals differential effects of glucagon-like peptide-1 and insulin on nutrient partitioning in ovine liver.

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.

Insulin-independent actions of glucagon-like peptide-1 in wethers.

Insulin-independent actions of glucagon-like peptide-1 (GLP-1) are not yet clear in ruminants. Four Suffolk mature wethers (60.0 ± 6.7 kg body weight (BW)) were intravenously infused with insulin (0.5 mU/kg BW/min; from 0 to 90 min) and GLP-1 (0.5 µg/kg BW/min; from 60 to 150 min) with both hormones co-administered from 60 to 90 min, in a repeated-measure design under euglycemic clamp for 150 min, to investigate whether GLP-1 has insulin-independent actions. Jugular blood samples were taken at 15-min intervals for plasma hormones and metabolites analysis. Compared to baseline concentrations (at 0 min), insulin infusion decreased (P < 0.05) plasma concentrations of glucagon, non-esterified fatty acids (NEFA), lactate, nonessential amino acids (NEAA), branched-chain amino acids (BCAA), total amino acids (TAA) and urea nitrogen (UN). Insulin plus GLP-1 infusion induced a greater increase (P < 0.05) in plasma concentrations of insulin and triglyceride (TG), but decreased (P < 0.05) glucagon, total cholesterol (T-Cho), NEAA and UN plasma concentrations. GLP-1 infusion increased (P < 0.05) NEFA, ß-hydroxybutyrate and TG, but decreased (P < 0.05) glucagon, T-Cho, NEAA, BCAA and UN plasma concentrations. In conclusion, GLP-1 exerts extrapancreatic roles in ruminants not only insulin-independent but probably, in contrast to non-ruminants, antagonistic to insulin effects.