GLP-1 promotes mitochondrial metabolism in vascular smooth muscle cells by enhancing endoplasmic reticulum–mitochondria coupling
Author
dc.contributor.author
Morales, Pablo E.
Author
dc.contributor.author
Torres, Gloria
es_CL
Author
dc.contributor.author
Sotomayor Torres, Cristian
es_CL
Author
dc.contributor.author
Peña Oyarzún, Daniel
es_CL
Author
dc.contributor.author
Rivera Mejías, Pablo
es_CL
Author
dc.contributor.author
Paredes, Felipe
es_CL
Author
dc.contributor.author
Chiong Lay, Mario
es_CL
Admission date
dc.date.accessioned
2014-12-30T19:41:14Z
Available date
dc.date.available
2014-12-30T19:41:14Z
Publication date
dc.date.issued
2014
Cita de ítem
dc.identifier.citation
Biochemical and Biophysical Research Communications 446 (2014) 410–416
en_US
Identifier
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DOI: 10.1016/j.bbrc.2014.03.004
Identifier
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https://repositorio.uchile.cl/handle/2250/121946
General note
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Artículo de publicación ISI
en_US
Abstract
dc.description.abstract
Incretin GLP-1 has important metabolic effects on several tissues, mainly through the regulation of
glucose uptake and usage. One mechanism for increasing cell metabolism is modulating endoplasmic
reticulum (ER)–mitochondria communication, as it allows for a more efficient transfer of Ca2+ into the
mitochondria, thereby increasing activity. Control of glucose metabolism is essential for proper vascular
smooth muscle cell (VSMC) function. GLP-1 has been shown to produce varied metabolic actions, but
whether it regulates glucose metabolism in VSMC remains unknown. In this report, we show that GLP-
1 increases mitochondrial activity in the aortic cell line A7r5 by increasing ER–mitochondria coupling.
GLP-1 increases intracellular glucose and diminishes glucose uptake without altering glycogen content.
ATP, mitochondrial potential and oxygen consumption increase at 3 h of GLP-1 treatment, paralleled
by increased Ca2+ transfer from the ER to the mitochondria. Furthermore, GLP-1 increases levels of
Mitofusin-2 (Mfn2), an ER-mitochondria tethering protein, via a PKA-dependent mechanism. Accordingly,
PKA inhibition and Mfn2 down-regulation prevented mitochondrial Ca2+ increases in GLP-1 treated
cells. Inhibiting both Ca2+ release from the ER and Ca2+ entry into mitochondria as well as diminishing
Mfn2 levels blunted the increase in mitochondrial activity in response to GLP-1. Altogether, these results
strongly suggest that GLP-1 increases ER–mitochondria communication in VSMC, resulting in higher
mitochondrial activity.
en_US
Patrocinador
dc.description.sponsorship
This research was funded in part by Comision Nacional de Ciencia
y Tecnologia (CONICYT), Chile (FONDECYT 1110180 to M.C.;
ANILLO ACT1111 to M.C.; FONDAP 15130011 to M.C.). P.M. holds
a CONICYT Master fellowship. G.T. and F.P. hold a CONICYT Ph.D.
fellowship.