In:
American Journal of Physiology-Endocrinology and Metabolism, American Physiological Society, Vol. 307, No. 2 ( 2014-07-15), p. E225-E236
Abstract:
Activation of AMP-activated protein kinase (AMPK) in cardiomyocytes induces translocation of glucose transporter GLUT4 and long-chain fatty acid (LCFA) transporter CD36 from endosomal stores to the sarcolemma to enhance glucose and LCFA uptake, respectively. Ca 2+ /calmodulin-activated kinase kinase-β (CaMKKβ) has been positioned directly upstream of AMPK. However, it is unknown whether acute increases in [Ca 2+ ] i stimulate translocation of GLUT4 and CD36 and uptake of glucose and LCFA or whether Ca 2+ signaling converges with AMPK signaling to exert these actions. Therefore, we studied the interplay between Ca 2+ and AMPK signaling in regulation of cardiomyocyte substrate uptake. Exposure of primary cardiomyocytes to inhibitors or activators of Ca 2+ signaling affected neither AMPK-Thr 172 phosphorylation nor basal and AMPK-mediated glucose and LCFA uptake. Despite their lack of an effect on substrate uptake, Ca 2+ signaling activators induced GLUT4 and CD36 translocation. In contrast, AMPK activators stimulated GLUT4/CD36 translocation as well as glucose/LCFA uptake. When cardiomyocytes were cotreated with Ca 2+ signaling and AMPK activators, Ca 2+ signaling activators further enhanced AMPK-induced glucose/LCFA uptake. In conclusion, Ca 2+ signaling shows no involvement in AMPK-induced GLUT4/CD36 translocation and substrate uptake but elicits transporter translocation via a separate pathway requiring CaMKKβ/CaMKs. Ca 2+ -induced transporter translocation by itself appears to be ineffective to increase substrate uptake but requires additional AMPK activation to effectuate transporter translocation into increased substrate uptake. Ca 2+ -induced transporter translocation might be crucial under excessive cardiac stress conditions that require supraphysiological energy demands. Alternatively, Ca 2+ signaling might prepare the heart for substrate uptake during physiological contraction by inducing transporter translocation.
Type of Medium:
Online Resource
ISSN:
0193-1849
,
1522-1555
DOI:
10.1152/ajpendo.00655.2013
Language:
English
Publisher:
American Physiological Society
Publication Date:
2014
detail.hit.zdb_id:
1477331-4
SSG:
12
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