Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/327766
Type: Artigo
Title: The Glp-1 Receptor Agonists Exenatide And Liraglutide Activate Glucose Transport By An Ampk-dependent Mechanism
Author: Andreozzi
Francesco; Raciti
Gregory Alexander; Nigro
Cecilia; Mannino
Gaia Chiara; Procopio
Teresa; Davalli
Alberto M.; Beguinot
Francesco; Sesti
Giorgio; Miele
Claudia; Folli
Franco
Abstract: Potentiation of glucose-induced insulin secretion is the main mechanism of exenatide (EXE) antidiabetic action, however, increased glucose utilization by peripheral tissues has been also reported. We here studied the effect of EXE on glucose uptake by skeletal muscle cells. Methods: 2-deoxy-glucose (2DG) uptake and intracellular signal pathways were measured in rat L6 skeletal muscle myotubes exposed to 100 nmol/l EXE for up to 48 h. Mechanisms of EXE action were explored by inhibiting AMPK activity with compound C (CC, 40 mu mol/l) or siRNAs (2 mu mol/l). Results: Time course experiments show that EXE increases glucose uptake up to 48 h achieving its maximal effect, similar to that induced by insulin, after 20 min (2-vs 2.5-fold-increase, respectively). Differently from insulin, EXE does not stimulate: (i) IR beta-subunit- and IRS1 tyrosine phosphorylation and binding to p85 regulatory subunit of PI-3kinase; (ii) AKT activation; and (iii) ERK1/2 and JNK1/2 phosphorylation. Conversely, EXE increases phosphorylation of alpha-subunit of AMPK at Thr172 by 2.5-fold (p < 0.01). Co-incubation of EXE and insulin does not induce additive effects on 2DG-uptake. Inhibition of AMPK with CC, and reduction of AMPK protein expression by siRNA, completely abolish EXE-induced 2DG-uptake. Liraglutide, another GLP-1 receptor agonist, also stimulates AMPK phosphorylation and 2DG-uptake. Moreover, EXE stimulates 2DG-uptake also by L6 myotubes rendered insulin-resistant with methylglyoxal. Finally, EXE also induces glucose transporter Glut-4 translocation to the plasma membrane. Conclusions/interpretation: In L6 myotubes, EXE and liraglutide increase glucose uptake in an insulin-independent manner by activating AMPK.
Subject: Exenatide
Liraglutide
Glucose Uptake
Ampk
Skeletal Muscle Cells
Insulin Signaling
Editor: Biomed Central Ltd
London
Rights: aberto
Identifier DOI: 10.1186/s12967-016-0985-7
Address: https://translational-medicine.biomedcentral.com.ez88.periodicos.capes.gov.br/articles/10.1186/s12967-016-0985-7
Date Issue: 2016
Appears in Collections:Unicamp - Artigos e Outros Documentos

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