grp40

Microglia are glial cells centrally related to pathophysiology and neuroimmunological regulation of pain through microglia-neuron crosstalk mechanisms. In contrast, anti-inflammatory mechanisms guided by immunological effectors such as IL-10 trigger the secretion of analgesic substances, culminating in the differential expression of genes encoding endogenous opioid peptides, especially β-endorphin. Thus, when β-endorphin binds to the µ-opioid receptor, it generates neuronal hyperpolarization, inhibiting nociceptive stimuli...

Myocardial hypertrophy is associated with a significant increase in intracellular Ca2+ , which can be induced by long-chain fatty acid. Palmitic acid methyl ester (PAME), a fatty acid ester released from adipose tissue, superior cervical ganglion, and retina, has been found to have anti-inflammation, antifibrosis, and peripheral vasodilation effects. However, the effects of PAME on cardiomyocytes are still unclear. The aim of this study was to determine whether PAME could disrupt the intracellular Ca2+ balance, leading to cardiomyocyte hypertrophy...

BACKGROUND: The disturbing incidence of type 2 diabetes mellitus (T2DM) enthused the development of newer antidiabetic targets with low toxicity and longer stability. In this respect, free fatty acid receptor 1 (FFAR1), also recognized as G protein-coupled receptor 40 (GPR40) is novel target for the treatment of T2DM. FFAR1/GPR40 have high level of expression in β-cells of pancreas and requirement of glucose for stimulating insulin release results in immense stimulation to utilise these targets in the medication of T2DM...

Rosiglitazone (RSG) can cause bone loss, however the mechanisms remain largely unknown. This study aims to investigate the effects of RSG on differentiation and mineralization of osteoblasts using primary cultured mouse fetal calvaria-derived osteoblasts as a model, and elucidate the receptor and signaling pathways responsible for these effects. We found that RSG suppressed the differentiation and mineralization of calvaria-derived osteoblasts. Peroxisome proliferators-activated receptor γ (PPARγ) siRNA significantly reversed the inhibitory effect of RSG on osteogenic differentiation...

The mechanisms linking fat intake to bone loss remain unclear. By demonstrating the expression of the free fatty acid receptor G-coupled protein receptor 40 (GPR40) in bone cells, we hypothesized that this receptor may play a role in mediating the effects of fatty acids on bone remodeling. Using micro-CT analysis, we showed that GPR40(-/-) mice exhibit osteoporotic features suggesting a positive role of GPR40 on bone density. In primary cultures of bone marrow, we showed that GW9508, a GRP40 agonist, abolished bone-resorbing cell differentiation...

Chronic exposure to elevated concentration of free fatty acids (FFA) has been verified to induce endoplasmic reticulum (ER) stress, which leads to pancreatic β-cell apoptosis. As one of the medium and long chain FFA receptors, GPR40 is highly expressed in pancreatic β cells, mediates both acute and chronic effects of FFA on β-cell function, but the role of GPR40 in FFA-induced β-cell apoptosis remains unclear. In this study, we investigated the possible effects of GPR40 in palmitate-induced MIN6 β-cell apoptosis, and found that DC260126, a novel small molecular antagonist of GPR40, could protect MIN6 β cells from palmitate-induced ER stress and apoptosis...

The G-protein coupled receptor 40 (GRP40) is a transmembrane receptor for free fatty acids, and is known for its relation to insulin secretion in the pancreas. Recent studies demonstrated that spatial memory and hippocampal long-term potentiation of rodents and cognitive function of humans are improved by a dietary supplementation with arachidonic and/or docosahexaenoic acids, which are possible ligands for GPR40. While free fatty acid effects on the brain might be related to GPR40 activation, the role of GPR40 in the central nervous system (CNS) is at present not known...