Insulin‐independent actions of glucagon‐like peptide‐1 in wethers

Abstract

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, β-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.

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

“…However, in our study the plasma insulin concentrations were kept constant by GLP‐1 infusion (El‐Sabagh et al . ), indicating a direct action of GLP‐1 on protein metabolism with no significant contribution of insulin. Also, it was reported that GLP‐1 exerts a protective effect against hepatocellular injuries (Klonoff et al .…”

“…These results are consistent with changes in blood profile reported in our previous publication (El‐Sabagh et al . ) where plasma concentrations of NEFA, BHBA and triglyceride were raised, but total cholesterol was decreased by GLP‐1 infusion. These results may suggest a physiological role for GLP‐1 in inducing lipid mobilization and oxidation, and this situation may be associated with ketogenesis and accumulation of cholesterol and sterols in liver.…”

“…Details of experimental design have been previously published (El‐Sabagh et al . ). Briefly, four Suffolk wethers (60.0 ± 6.7 kg body weight (BW)), kept in metabolism crates and receiving a maintenance diet (National Research Council (NRC) ) consistsing of alfalfa hay and barely (7:3) twice a day at 09.00 and 17.00 hours, were used in a repeated‐measure design under euglycemic‐hyperinsulinemic and hyper GLP‐1 clamps for 150 min to determine the metabolic responses to insulin and GLP‐I infusion.…”

“…In our experiment in wethers, it was observed that GLP‐1 infusion induced elevations in blood concentrations of non‐esterified fatty acids (NEFA), β‐hydroxybutyrate (BHBA) and triglyceride, but decreased the total cholesterol (El‐Sabagh et al . ); typical differential effects to insulin implies that GLP‐1 actions are not only insulin‐independent but probably antagonize insulin actions. However, the insulin‐independent and/or insulin‐antagonistic actions of GLP‐1 in ruminants need to be thoroughly explored because very little work has been conducted to define the specific roles of GLP‐1 in ruminant liver.…”

“…Therefore, the aim of this study was to gain further insights into the insulin‐independent actions of GLP‐1 at a metabolomic level through exploring the changes in metabolic pathways involved in GLP‐1 regulation of nutrient partitioning by the liver, with the aim to draw further understanding of previous results observed (El‐Sabagh et al . , ). Identifying metabolites associated with insulin‐independent actions of GLP‐1 in ruminants would advance our understanding of the role of gut hormones in nutrient partitioning and its integration with metabolism and animal health.…”