Sensitization and translocation of TRPVI by insulin and IGF-I

Abstract

Insulin and insulin-like growth factors (IGFs) maintain vital neuronal functions. Absolute or functional deficiencies of insulin or IGF-I may contribute to neuronal and vascular complications associated with diabetes. Vanilloid receptor I (also called TRPVI) is an on channel that mediates inflammatory thermal nociception and is present on sensory neurons. Here we demonstrate that both insulin and IGF-I enhance TRPVI-mediated membrane currents in heterologous expression systems and cultured dorsal root ganglion neurons. Enhancement of membrane current results from both increased sensitivity of the receptor and translocation of TRPVI from cytosol to plasma membrane. Receptor tyrosine kinases trigger a signaling cascade leading to activation of phosphatidylinositol 3-kinase (PI(3)K) and protein kinase C (PKC)-mediated phosphorylation of TRPV 1, which is found to be essential for the potentiation. These findings establish a link between the insulin family of trophic factors and vanilloid receptors. © 2005 Van Buren et al; licensee BioMed Central Ltd.