Diaz-Garcia Carlos Manlio, Morales-Lázaro Sara L, Sánchez-Soto Carmen, Velasco Myrian, Rosenbaum Tamara, Hiriart Marcia
División de Neurociencias, Departamento de Neurodesarrollo y Fisiología, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Circuito Exterior S/N Avenida Universidad, Ciudad Universitaria, CP 04510, Coyoacán, Mexico DF, Mexico.
J Membr Biol. 2014 Jun;247(6):479-91. doi: 10.1007/s00232-014-9658-8. Epub 2014 Mar 28.
Transient receptor potential channels have been put forward as regulators of insulin secretion. A role for the TRPV1 ion channel in insulin secretion has been suggested in pancreatic beta cell lines. We explored whether TRPV1 is functionally expressed in RINm5F and primary beta cells from neonate and adult rats. We examined if capsaicin could activate cationic non-selective currents. Our results show that TRPV1 channels are not functional in insulin-secreting cells, since capsaicin did not produce current activation, not even under culture conditions known to induce the expression of other ion channels in these cells. Although TRPV1 channels seem to be irrelevant for the physiology of isolated beta cells, they may play a role in glucose homeostasis acting through the nerve fibers that regulate islet function. At the physiological level, we observed that Trpv1 (-/-) mice presented lower fasting insulin levels than their wild-type littermates, however, we did not find differences between these experimental groups nor in the glucose tolerance test or in the insulin secretion. However, we did find that the Trpv1 (-/-) mice exhibited a higher insulin sensitivity compared to their wild-type counterparts. Our results demonstrate that TRPV1 does not contribute to glucose-induced insulin secretion in beta cells as was previously thought, but it is possible that it may control insulin sensitivity.
瞬时受体电位通道已被提出作为胰岛素分泌的调节因子。在胰腺β细胞系中,TRPV1离子通道在胰岛素分泌中的作用已被提出。我们探究了TRPV1在新生大鼠和成年大鼠的RINm5F细胞及原代β细胞中是否有功能性表达。我们检测了辣椒素是否能激活阳离子非选择性电流。我们的结果表明,TRPV1通道在胰岛素分泌细胞中无功能,因为辣椒素并未引起电流激活,即使在已知能诱导这些细胞中其他离子通道表达的培养条件下也未激活。尽管TRPV1通道似乎与分离的β细胞的生理学无关,但它们可能通过调节胰岛功能的神经纤维在葡萄糖稳态中发挥作用。在生理水平上,我们观察到Trpv1(-/-)小鼠的空腹胰岛素水平低于其野生型同窝小鼠,然而,我们在这些实验组之间以及在葡萄糖耐量试验或胰岛素分泌方面均未发现差异。但是,我们确实发现Trpv1(-/-)小鼠与野生型小鼠相比表现出更高的胰岛素敏感性。我们的结果表明,TRPV1并不像之前认为的那样参与β细胞中葡萄糖诱导的胰岛素分泌,但它有可能控制胰岛素敏感性。