| Autor: |
Fedorenko, Olena A., Pulbutr, Pawitra, Banke, Elin, Akaniro-Ejim, Nneoma E., Bentley, Donna C., Olofsson, Charlotta S., Sue Chan, Smith, Paul A. |
| Předmět: |
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| Zdroj: |
Journal of Endocrinology; Feb2020, Vol. 244 Issue 2, p369-381, 13p |
| Abstrakt: |
L-type channel antagonists are of therapeutic benefit in the tre atment of hyperlipidaemia and insulin resistance. Our aim was to identify L-type voltage-gated Ca2+ channels in white fat adipocytes, and determine if they affect i ntracellular Ca2+, lipolysis and lipogenesis. We used a multidisciplinary approach of molecular biology, confocal microscopy, Ca2+ imaging and metabolic assays to explore this problem using adipocytes isolated from adult rat epididymal fat pads. CaV1.2, CaV1.3 and CaV1.1 alpha1, beta and alpha2delta subunits were detected at the gene expression level. The CaV1.2 and CaV1.3 alpha1 subunits were identified in the plasma membrane at the pr otein level. Confocal microscopy with fluorescent antibodies labelled CaV1.2 in the pl asma membrane. Ca2+ imaging revealed that the intracellular Ca2+ concentration, [Ca2+]i was reversibly decreased by removal of extracellular Ca2+, an effect mimicked by verapamil, nifedipine and Co2+, all blockers of L-type channels, whereas the Ca2+ channel agonist BAY-K8644 increased [Ca2+]i. The finding that the magnitude of these effects correlated with basal [Ca2+]i suggests that adipocyte [Ca2+]i is controlled by L-type Ca2+ channels that are constitutively active at the adipocyte depolarized membrane potential. Pharmacological manipulation of L-type channel activity modulated both basal and catecholaminestimulated lipolysis but not insulin-induced glucose uptake or lipogenesis. We conclude that white adipocytes have constitutively active L-type Ca2+ channels which explains their sensitivity of lipolysis to Ca2+ channel modulators. Our data suggest CaV1.2 as a potential novel therapeutic target in the treatment of obesity. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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