In conclusion GPR inhibits and GPR enhances the

In conclusion, GPR120 inhibits and GPR40 enhances the cell motile activity stimulated by TPA in melanoma cells, while MMP-9 activation was reduced by GPR40. In contrast, GPR40 negatively regulated cellular functions of fibrosarcoma ache inhibitor [11]. Taken together, it is suggested that opposite effects of GPR120 and GPR40 are involved in the regulation of cellular functions, dependent on types of cells. We are currently investigating whether GPR120 and GPR40 may contribute to acquisition of chemo-resistance in melanoma cells.
Conflict of interest statement
Acknowledgements This work was supported by JSPS KAKENHI Grant Number 24590493 and by Grants from the Faculty of Science and Engineering, Kindai University.
Introduction G protein-coupled receptor 120 (GPR120) is one of the plasma membrane receptors for free fatty acids (FFAs), and it can be activated by unsaturated long-chain FFAs. GPR120 activation stimulated glucagon like peptide-1 (GLP-1) secretion from intestine enteroendocrine cells (Hirasawa et al., 2005), and moreover, GPR120 activation protected enteroendocrine cell line STC-1 against apoptosis (Katsuma et al., 2005). GPR120 was also reported to stimulate cholecystokinin secretion (Tanaka et al., 2008). More interestingly, it is suggested that GPR120 activation alleviates inflammation in fat tissue and improves insulin sensitization of mice (Oh et al., 2010). Recent studies showed that GPR120 exerts a role in control of obesity (Ichimura et al., 2012, McLarnon, 2012), and it is postulated that GPR120 signaling plays an important role in the metabolic syndrome and diabetes mellitus (Oh and Olefsky, 2012). To further understand the function of GPR120 in metabolism, it is worthy to clarify the distribution of GPR120 in body tissues. It has been reported that GPR120 is expressed in the mouse intestine, lung and adipose tissue (Miyauchi et al., 2009). A recent report indicates that GPR120 is expressed in human pancreatic islets (Taneera et al., 2012). Pancreas performs a vital role in the fuel and energy metabolism and is essential for the occurrence of diabetes mellitus. One type of plasma membrane receptor for FFAs, GPR40, has been first discovered in pancreas and considered to mediate FFAs-enhanced insulin secretion (Alquier et al., 2009, Briscoe et al., 2003, Ferdaoussi et al., 2012, Itoh et al., 2003). Although it is suggested that GPR120 expresses in human islets and protects islets from apoptosis (Taneera et al., 2012), the phenotypes of GPR120-positive cells in pancreas has not been known. The present study observed the expression of GPR120 in rat and human pancreas and further identified the phenotypes of GPR120-positive cells in human and rat pancreas.
Materials and methods
Results
Discussion The first FFAs plasma membrane receptor found in pancreas is GPR40, and its expression is localized in islets, mainly on beta-cells (Itoh et al., 2003). Our present study found the expression of the other FFAs receptor GPR120 in pancreas. Interestingly, GPR120 is mainly expressed in the interstitial tissue of pancreas. To verify the specificity of the staining, we used two different antibodies of GPR120, which were from Sigma–Aldrich and Novus Biological. Both antibodies stained the pancreas with high specificity to some kinds of pancreatic cells that displayed in pancreas with specific pattern. There was low background for each antibody. Moreover, after absorption by GPR120 protein, the antibodies could not perform positive staining. These results indicate that the staining is specific and reliable. We further checked the antibodies in rat intestine tissues and found the specific staining of enteroendocrine cells in intestine, which is same to the previous report (Hirasawa et al., 2005). This result also support the specificity of antibodies used in this study. GPR120-positive cells were distributed mainly in the interstitial tissue of pancreas, and therefore we next observed the expression of some markers of a few kinds of cells that distribute in the interstitial tissues and in the blood vessels. Nestin and vimentin are markers of stellate cells and mesenchymal cells (Datar and Bhonde, 2009, Lardon et al., 2002, Omary et al., 2004, Omary et al., 2007). We found the distribution of nestin-positive cells and vimentin-positive cells in the interstitial tissues of pancreas. However, they were not colocolized with GPR120, suggesting that GPR120-positive cells were not pancreatic stellate cells or mesenchymal cells. Alpha-SMA was the marker of vascular smooth muscle cells (Gabbiani et al., 1981). We found its specific expression in pancreas and the structure of vessels formed by α-SMA-positive staining. However, we did not found the colocalization of GPR120 with α-SMA, indicating that GPR120-positive cells are not vascular smooth muscle cells. A recent report indicates that GPR120 is expressed in human islets (Taneera et al., 2012). We used glucagon staining to show the location of islets in human and rat pancreas and performed the double-staining with GPR120, and we did not found the distribution of GPR120 positive cells in islets and colocalization with glucagon. The reason for the discrepancy to previous report may be the low levels of GPR120 expression in islets. GPR120 expression in islets at protein levels may be too low to be detected in our immunohistochemical staining system. Another reason may be due to the difference in the samples we used. As we used the pancreatic tissues from the donor with adinocarcinoma, it may be different to the tissues from the cadaver donors used in the study by Taneera et al. Further investigation is needed to clarify GPR120 expression in islets.