In:
American Journal of Physiology-Endocrinology and Metabolism, American Physiological Society, Vol. 294, No. 6 ( 2008-06), p. E1178-E1186
Abstract:
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 Ca 2+ and increase voltage-gated Ca 2+ 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 Ca 2+ 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 α 1 -subunits (β-cell Cav1.3 or lung Cav1.2) and ERFP-tagged islet β-subunits (iβ 2a or iβ 3 ). In COS-7 cells, elevations in intracellular Ca 2+ mediated by LTCC were enhanced by an oleate-BSA complex. To extend these findings, Ca 2+ current was measured in LTCC-expressing HEK-293 cells that revealed an increase in peak Ca 2+ current within 2 min 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 Ca 2+ channel modulation. These results show for the first time that two L-type Ca 2+ 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.
Type of Medium:
Online Resource
ISSN:
0193-1849
,
1522-1555
DOI:
10.1152/ajpendo.90237.2008
Language:
English
Publisher:
American Physiological Society
Publication Date:
2008
detail.hit.zdb_id:
1477331-4
SSG:
12
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