Effect of glucagon-like peptide-1 and ghrelin on liver metabolites in steers

2014 ◽  
Vol 54 (10) ◽  
pp. 1732 ◽  
Author(s):  
M. El-Sabagh ◽  
D. Taniguchi ◽  
T. Sugino ◽  
T. Obitsu ◽  
K. Taniguchi

Glucagon-like peptide 1 (GLP-1) and ghrelin have opposite regulatory effects on glucose metabolism in non-ruminants. However, mechanisms by which GLP-1 and ghrelin regulate nutrient partitioning, particularly in the liver, have been much less demonstrated in ruminants. A novel metabolomic method based on capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS) combined with multivariate statistical analysis was applied to address the GLP-1 and ghrelin-induced metabolic changes in the liver of steers. Three Holstein steers (400 ± 5.0 kg LW) fed a maintenance diet according to Japanese feeding standards were randomly assigned to three treatments (GLP-1, ghrelin and saline) in a 3 × 3 Latin square design with one week apart. Liver biopsies were taken 30 min after a single injection (1.0 μg/kg LW) of GLP-1 or ghrelin, and analysed for metabolites by Agilent CE-TOFMS system. Also, blood samples were collected for plasma hormones analysis. Results indicated that 20 and 10 liver metabolites were altered (P < 0.05) by GLP-1 and ghrelin, respectively. Pathway analysis showed that GLP-1 is involved in biochemical pathways related to glycolysis/gluconeogenesis, lipogenesis and lipid export from the liver, oxidative stress defence and protein turnover. Ghrelin was shown to be involved in pathways related to glycolysis, protein anabolism and phospholipid biosynthesis. However, plasma concentrations of insulin, growth hormone and glucagon did not differ between treatments. These results imply that GLP-1 and ghrelin are involved in multibiochemical pathways that go beyond simply regulating glucose metabolism. In addition, the effects of GLP-1 and ghrelin may potentially be independent of insulin and growth hormone, respectively.

2013 ◽  
Vol 304 (7) ◽  
pp. E677-E685 ◽  
Author(s):  
Melissa A. Burmeister ◽  
Jennifer Ayala ◽  
Daniel J. Drucker ◽  
Julio E. Ayala

Glucagon-like peptide-1 (GLP-1) suppresses food intake via activation of a central (i.e., brain) GLP-1 receptor (GLP-1R). Central AMP-activated protein kinase (AMPK) is a nutrient-sensitive regulator of food intake that is inhibited by anorectic signals. The anorectic effect elicited by hindbrain GLP-1R activation is attenuated by the AMPK stimulator AICAR. This suggests that central GLP-1R activation suppresses food intake via inhibition of central AMPK. The present studies examined the mechanism(s) by which central GLP-1R activation inhibits AMPK. Supporting previous findings, AICAR attenuated the anorectic effect elicited by intracerebroventricular (icv) administration of the GLP-1R agonist exendin-4 (Ex-4). We demonstrate that Ex-4 stimulates glycolysis and suppresses AMPK phosphorylation in a glucose-dependent manner in hypothalamic GT1-7 cells. This suggests that inhibition of AMPK and food intake by Ex-4 requires central glucose metabolism. Supporting this, the glycolytic inhibitor 2-deoxyglucose (2-DG) attenuated the anorectic effect of Ex-4. However, icv glucose did not enhance the suppression of food intake by Ex-4. AICAR had no effect on Ex-4-mediated reduction in locomotor activity. We also tested whether other carbohydrates affect the anorectic response to Ex-4. Intracerebroventricular pretreatment with the sucrose metabolite fructose, an AMPK activator, attenuated the anorectic effect of Ex-4. This potentially explains the increased food intake observed in sucrose-fed mice. In summary, we propose a model whereby activation of the central GLP-1R reduces food intake via glucose metabolism-dependent inhibition of central AMPK. We also suggest that fructose stimulates food intake by impairing central GLP-1R action. This has significant implications given the correlation between sugar consumption and obesity.


2018 ◽  
Vol 28 (6) ◽  
pp. 602-610
Author(s):  
Linn Bøhler ◽  
Sílvia Ribeiro Coutinho ◽  
Jens F. Rehfeld ◽  
Linda Morgan ◽  
Catia Martins

Active, as opposed to inactive, individuals are able to adjust their energy intake after preloads of different energy contents. The mechanisms responsible for this remain unknown. This study examined differences in plasma concentration of appetite-related hormones in response to breakfasts of different energy contents, between active and inactive men. Sixteen healthy nonobese (body mass index = 18.5–27 kg/m2) adult males (nine active and seven inactive) participated in this study. Participants were given a high-energy (570 kcal) or a low-energy (205 kcal) breakfast in a random order. Subjective feelings of appetite and plasma concentrations of active ghrelin, active glucagon-like peptide-1, total peptide YY (PYY), cholecystokinin, and insulin were measured in fasting and every 30 min up to 2.5 hr, in response to both breakfasts. Mixed analysis of variance (fat mass [in percentage] as a covariate) revealed a higher concentration of active ghrelin and lower concentration of glucagon-like peptide-1, and cholecystokinin after the low-energy breakfast (p < .001 for all). Postprandial concentration of PYY was greater after the high energy compared with the low energy, but for inactive participants only (p = .014). Active participants had lower postprandial concentrations of insulin than inactive participants (p < .001). Differences in postprandial insulin between breakfasts were significantly lower in active compared with inactive participants (p < .001). Physical activity seems to modulate the postprandial plasma concentration of insulin and PYY after the intake of breakfasts of different energy contents, and that may contribute, at least partially, to the differences in short-term appetite control between active and inactive individuals.


2015 ◽  
Vol 593 (9) ◽  
pp. 2185-2198 ◽  
Author(s):  
Kim A. Sjøberg ◽  
Stephen Rattigan ◽  
Jacob F. Jeppesen ◽  
Anne-Marie Lundsgaard ◽  
Jens J. Holst ◽  
...  

Diabetes ◽  
2013 ◽  
Vol 63 (2) ◽  
pp. 483-493 ◽  
Author(s):  
M. Shah ◽  
J. H. Law ◽  
F. Micheletto ◽  
M. Sathananthan ◽  
C. Dalla Man ◽  
...  

1991 ◽  
Vol 129 (1) ◽  
pp. 55-58 ◽  
Author(s):  
A. Faulkner ◽  
H. T. Pollock

ABSTRACT The effects of i.v. glucagon-like peptide-1-(7–36)amide (GLP-1; 10 μg) on starved sheep given an i.v. glucose load (5 g) were studied. Plasma insulin concentrations rose significantly more after glucose administration in fed than in starved sheep. Giving GLP-1 to starved sheep increased the insulin response to the glucose load. The rise in plasma insulin concentrations in starved sheep given GLP-1 was similar to that observed in fed sheep. Plasma glucose concentrations returned to normal values more quickly in the starved sheep given GLP-1 than in starved sheep not given gut hormone. Plasma concentrations of free fatty acid, urea and α-amino nitrogen decreased more quickly following glucose administration in starved sheep given GLP-1 than in those not given GLP-1. The data suggest a role for GLP-1 in regulating plasma insulin concentrations and hence metabolism in ruminant animals. The possible role of gut hormones in ruminants is discussed. Journal of Endocrinology (1991) 129, 55–58


2002 ◽  
Vol 173 (3) ◽  
pp. 465-473 ◽  
Author(s):  
MA Luque ◽  
N Gonzalez ◽  
L Marquez ◽  
A Acitores ◽  
A Redondo ◽  
...  

Glucagon-like peptide-1 (GLP-1) has been shown to have insulin-like effects upon the metabolism of glucose in rat liver, muscle and fat, and on that of lipids in rat and human adipocytes. These actions seem to be exerted through specific receptors which, unlike that of the pancreas, are not - at least in liver and muscle - cAMP-associated. Here we have investigated the effect, its characteristics, and possible second messengers of GLP-1 on the glucose metabolism of human skeletal muscle, in tissue strips and primary cultured myocytes. In muscle strips, GLP-1, like insulin, stimulated glycogen synthesis, glycogen synthase a activity, and glucose oxidation and utilization, and inhibited glycogen phosphorylase a activity, all of this at physiological concentrations of the peptide. In cultured myotubes, GLP-1 exerted, from 10(-13) mol/l, a dose-related increase of the D-[U-(14)C]glucose incorporation into glycogen, with the same potency as insulin, together with an activation of glycogen synthase a; the effect of 10(-11) mol/l GLP-1 on both parameters was additive to that induced by the equimolar amount of insulin. Synthase a was still activated in cells after 2 days of exposure to GLP-1, as compared with myotubes maintained in the absence of peptide. In human muscle cells, exendin-4 and its truncated form 9-39 amide (Ex-9) are both agonists of the GLP-1 effect on glycogen synthesis and synthase a activity; but while neither GLP-1 nor exendin-4 affected the cellular cAMP content after 5-min incubation in the absence of 3-isobutyl-1-methylxantine (IBMX), an increase was detected with Ex-9. GLP-1, exendin-4, Ex-9 and insulin all induced the prompt hydrolysis of glycosylphosphatidylinositols (GPIs). This work shows a potent stimulatory effect of GLP-1 on the glucose metabolism of human skeletal muscle, and supports the long-term therapeutic value of the peptide. Further evidence for a GLP-1 receptor in this tissue, different from that of the pancreas, is also illustrated, suggesting a role for an inositolphosphoglycan (IPG) as at least one of the possible second messengers of the GLP-1 action in human muscle.


2016 ◽  
Vol 94 (suppl_5) ◽  
pp. 549-550
Author(s):  
Y. Inabu ◽  
A. Saegusa ◽  
K. Inouchi ◽  
M. Oba ◽  
T. Sugino

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