| Autor: |
Yingrao Tian, Corkey, Richard F., Yaney, Gordon C., Goforth, Paula B., Satin, Leslie S., De Vargas, Lina Moitoso |
| Předmět: |
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| Zdroj: |
American Journal of Physiology: Endocrinology & Metabolism; Jun2008, Vol. 294, pE1178-E1186, 9p, 11 Graphs |
| Abstrakt: |
Nonesterified fatty acids such as oleate and palmitate acutely potentiate insulin secretion from pancreatic islets in a glucose-dependent manner. In addition, recent studies show that fatty acids elevate intracellular free Ca2+ and increase voltage-gated Ca2+ current in mouse β-cells, although the mechanisms involved are poorly understood. Here we utilized a heterologous system to express subunit-defined voltage-dependent L-type Ca2+ channels (LTCC) and demonstrate that β-cell calcium may increase in part from an interaction between fatty acid and specific calcium channel subunits. Distinct functional LTCC were assembled in both COS-7 and HEK-293 cells by expressing either one of the EYFP-tagged L-type α1-subunits (β-cell Cav1.3 or lung Cav1.2) and ERFP-tagged islet β-subunits (iβ2a or iβ3). In COS-7 cells, elevations in intracellular Ca2+ mediated by LTCC were enhanced by an oleate-BSA complex. To extend these findings, Ca2+ current was measured in LTCC-expressing HEK-293 cells that revealed an increase in peak Ca2+ current within 2 mm after addition of the oleate complex, with maximal potentiation occurring at voltages <0 mV. Both Cav1.3 and Cav1.2 were modulated by oleate, and the presence of different auxiliary β-subunits resulted in differential augmentation. The potentiating effect of oleate on Cav1.2 was abolished by the pretreatment of cells with triacsin C, suggesting that long-chain CoA synthesis is necessary for Ca2+ channel modulation. These results show for the first time that two L-type Ca2+ channels expressed in β-cells (Cav1.3 and Cav1.2) appear to be targeted by nonesterified fatty acids. This effect may account in part for the acute potentiation of glucose-dependent insulin secretion by fatty acids. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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