GLP-1 promotes mitochondrial metabolism in vascular smooth muscle cells by enhancing endoplasmic reticulum-mitochondria coupling

Morales, Pablo E; Torres, Gloria; Sotomayor-Floresc Cristian; Peña-Oyarzún, Daniel; Rivera-Mejías, Pablo; Paredes, felipe; Chiong, Mario

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 PICA-dependent mechanism. Accordingly, PICA 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. (c) 2014 Elsevier Inc. All rights reserved.

Más información

Título según WOS: GLP-1 promotes mitochondrial metabolism in vascular smooth muscle cells by enhancing endoplasmic reticulum-mitochondria coupling
Título según SCOPUS: GLP-1 promotes mitochondrial metabolism in vascular smooth muscle cells by enhancing endoplasmic reticulum-mitochondria coupling
Título de la Revista: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volumen: 446
Número: 1
Editorial: ACADEMIC PRESS INC ELSEVIER SCIENCE
Fecha de publicación: 2014
Página de inicio: 410
Página final: 416
Idioma: English
DOI:

10.1016/j.bbrc.2014.03.004

Notas: ISI, SCOPUS - ISI