scholarly journals Retinal Pigment Epithelial Cells Express a Functional Receptor for Glucagon-Like Peptide-1 (GLP-1)

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Alessandra Puddu ◽  
Roberta Sanguineti ◽  
Fabrizio Montecucco ◽  
Giorgio L. Viviani
Keyword(s):  
Protein Kinase ◽  
Biological Effects ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Growth Factor Receptor ◽  
Retinal Pigment Epithelial Cells ◽  
Mitogen Activated Protein Kinase ◽  
Wide Range ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glucagon-like peptide-1 (GLP-1) is a gut-derived incretin hormone that has been shown to improve glucose homeostasis in type 2 diabetes. The biological effects of GLP-1 are mediated by its specific receptor GLP-1R that is expressed in a wide range of tissues, where it is responsible of the extra-pancreatic effects of GLP-1. Since the retinal pigment epithelium (RPE), that forms the outer retinal barrier, has a key role in protecting from diabetic retinopathy (DR), we investigated the potential expression and function of GLP-1R in a RPE cell line. ARPE-19 cells were cultured in DMEM/F12 supplemented with 10% FBS. The expression of GLP-1R was evaluated at both mRNA and protein levels. Then, the activation postreceptor intracellular signal transduction pathways (extracellular signal-regulated kinases 1 and 2 [ERK1/2] and protein kinase B [PKB]) were assessed by western blot in normal cells or silenced for GLP-1R in the presence or absence of 10 nmol/L GLP-1. The potential connections between intracellular signalling pathways triggered by GLP-1 stimulation were performed before incubating cells with kinase pharmacological inhibitors of mitogen-activated protein kinase (MEK)1/2, phosphatydilinositol-3kinase (PI3K), or epidermal growth factor receptor (EGFR). The results showed that GLP1R is expressed at both mRNA and protein level in ARPE-19 cells. Stimulation with GLP-1 strongly activated PKB and ERK1/2 phosphorylation till 40 min of exposure. GLP-1-mediated activation of both kinases was dependent on the upstream activation of PI3K and EGFR. Finally, treatment with GLP-1 did not affect the spontaneous release of VEGF-A from ARPE-19 cells. In conclusion, this paper showed that the presence of functional GLP-1R is expressed in RPE cells. These data might represent the rationale to further investigate the potential direct beneficial effects of GLP-1 treatment against DR.

Myeloid-Derived Growth Factor Promotes Intestinal Glucagon-Like Peptide-1 Production in Male Mice With Type 2 Diabetes

Endocrinology ◽  
2020 ◽  
Vol 161 (2) ◽  
Author(s):  
Li Wang ◽  
Yixiang Li ◽  
Bei Guo ◽  
Jiajia Zhang ◽  
Biao Zhu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Growth Factor ◽  
Protein Kinase ◽  
Cardiac Myocyte ◽  
Glycogen Synthase ◽  
Mitogen Activated Protein Kinase ◽  
Positive Effects ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract Myeloid-derived growth factor (MYDGF), which is produced by bone marrow–derived cells, mediates cardiac repair following myocardial infarction by inhibiting cardiac myocyte apoptosis to subsequently reduce the infarct size. However, the function of MYDGF in the incretin system of diabetes is still unknown. Here, loss-of-function and gain-of-function experiments in mice revealed that MYDGF maintains glucose homeostasis by inducing glucagon-like peptide-1 (GLP-1) production and secretion and that it improves glucose tolerance and lipid metabolism. Treatment with recombinant MYDGF increased the secretion and production of GLP-1 in STC-1 cells in vitro. Mechanistically, the positive effects of MYDGF are potentially attributable to the activation of protein kinase A/glycogen synthase kinase 3β/β-catenin (PKA/GSK-3β/β-catenin) and mitogen-activated protein kinase (MAPK) kinases/extracellular regulated protein kinase (MEK/ERK) pathways. Based on these findings, MYDGF promotes the secretion and production of GLP-1 in intestinal L-cells and potentially represents a potential therapeutic medication target for type 2 diabetes.

PKC isoenzymes differentially modulate the effect of thrombin on MAPK-dependent RPE proliferation

2008 ◽  
Vol 28 (6) ◽  
pp. 307-317 ◽  
Author(s):  
Jose P. Palma-Nicolas ◽  
Edith López ◽  
Ana María López-Colomé
Keyword(s):  
Cell Proliferation ◽  
Protein Kinase ◽  
Mapk Pathway ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Traumatic Injury ◽  
Mitogen Activated Protein Kinase ◽  
Erk Phosphorylation ◽  
Pkc Isoforms ◽  
Stimulation Of

Thrombin signalling through PAR (protease-activated receptor)-1 is involved in cellular processes, such as proliferation, differentiation and cell survival. Following traumatic injury to the eye, thrombin signalling may participate in disorders, such as PVR (proliferative vitreoretinopathy), a human eye disease characterized by the uncontrolled proliferation, transdifferentiation and migration of otherwise quiescent RPE (retinal pigment epithelium) cells. PARs activate the Ras/Raf/MEK/ERK MAPK pathway (where ERK is extracellular-signal-regulated kinase, MAPK is mitogen-activated protein kinase and MEK is MAPK/ERK kinase) through the activation of Gα and Gβγ heterotrimeric G-proteins, and the downstream stimulation of the PLC (phospholipase C)-β/PKC (protein kinase C) and PI3K (phosphoinositide 3-kinase) signalling axis. In the present study, we examined the molecular signalling involved in thrombin-induced RPE cell proliferation, using rat RPE cells in culture as a model system for PVR pathogenesis.  Our results showed that thrombin activation of PAR-1 induces RPE cell proliferation through Ras-independent activation of the Raf/MEK/ERK1/2 MAPK signalling cascade. Pharmacological analysis revealed that the activation of ‘conventional’ PKC isoforms is essential for proliferation, although thrombin-induced phosphorylation of ERK1/2 requires the activation of atypical PKCζ by PI3K. Consistently, thrombin-induced ERK1/2 activation and RPE cell proliferation were prevented completely by PI3K or PKCζ inhibition. These results suggest that thrombin induces RPE cell proliferation by joint activation of PLC-dependent and atypical PKC isoforms and the Ras-independent downstream stimulation of the Raf/MEK/ERK1/2 MAPK cascade. The present study is the first report demonstrating directly thrombin-induced ERK phosphorylation in the RPE, and the involvement of atypical PKCζ in this process.

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