BINDING AND ACTIVATION OF G PROTEIN-COUPLED RECEPTOR 40 BY PERFLUORODECANOIC ACID
Lianying Zhang, Xinjun Zhu, Junxiao Xu
Abstract
Perfluoroalkyl acids (PFAAs) have been shown to disrupt insulin
secretion in animals, and are significantly related to serum insulin
concentration and diabetes incidence in several epidemiological
studies. G-protein coupled receptor 40 (GRP40) is a transmembrane
receptor and is activated by medium- and long-chain fatty acid. This
receptor plays an important role in insulin secretion. In this study, the
direct binding interactions between perfluorodecanoic acid (PFDA)
and GPR40 and the subsequent alteration of GPR40 activity were
investigated. The results indicated that PFDA could bind GPR40
directly with a Kd of 2.70 μM. The [Ca2+]i assay indicated that the
PFDA was able to induce the elevation of [Ca2+]i, and the GW1100
could inhibit entirely the PFDA-induced [Ca2+]i increasing, indicating
that the [Ca2+]i increasing induced by PFDA in this study was GRP40-
mediated. This study showed the PFDA could directly bind GPR40
and activate the signal pathway