Leptin Induces Proliferation of Pancreatic β Cell Line MIN6 through Activation of Mitogen-Activated Protein Kinase

1997 ◽  
Vol 241 (3) ◽  
pp. 765-768 ◽  
Author(s):  
Katsuya Tanabe ◽  
Shigeru Okuya ◽  
Yukio Tanizawa ◽  
Akira Matsutani ◽  
Yoshitomo Oka
Keyword(s):  
Protein Kinase ◽  
Cell Line ◽  
Mitogen Activated Protein Kinase ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Mitogen Activated Protein

scholarly journals Visfatin inhibits apoptosis of pancreatic β-cell line, MIN6, via the mitogen-activated protein kinase/phosphoinositide 3-kinase pathway

2011 ◽  
Vol 47 (1) ◽  
pp. 13-21 ◽  
Author(s):  
Qun Cheng ◽  
Weipin Dong ◽  
Lei Qian ◽  
Jingcheng Wu ◽  
Yongde Peng
Keyword(s):  
Cell Proliferation ◽  
Protein Kinase ◽  
Signaling Pathways ◽  
Cell Line ◽  
Cell Apoptosis ◽  
Mitogen Activated Protein Kinase ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Mitogen Activated Protein ◽  
Phosphoinositide 3 Kinase

Visfatin is an adipocytokine that plays an important role in attenuating insulin resistance by binding to insulin receptor. It has been suggested that visfatin plays a role in the regulation of cell apoptosis and inflammation by an as yet unidentified mechanism. This study investigated the protective effects of visfatin on palmitate-induced islet β-cell apoptosis in the clonal mouse pancreatic β-cell line MIN6. The cells were treated with palmitate and/or recombinant visfatin. An 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan assay was used to detect cell proliferation, V-FITC/propidium iodide staining was used to measure cell apoptosis and necrosis, and western blot analysis was used to detect the expression of proapoptotic proteins. The incubation of the cells with visfatin led to a concentration-dependent increase of cell proliferation (1.55-fold at 10−7 M and 24 h compared with control,P<0.05). Visfatin significantly reduced the cell apoptosis induced by palmitate and caused a significant change in the expression of several proapoptotic proteins, including upregulation of Bcl-2 and a marked downregulation of cytochromecand caspase 3. Visfatin also activated the ERK1/2 and the phosphoinositide 3-kinase (PI3K)/AKT signaling pathways in a time- and concentration-dependent manner, and the effect of visfatin on apoptosis was blocked by the specific ERK1/2 and PI3K/AKT inhibitors, PD098059 and LY294002. We conclude that visfatin can increase β-cell proliferation and prevent apoptosis, activate intracellular signaling, and regulate the expression of proapoptotic proteins. The antiapoptotic action of visfatin is mediated by activation of mitogen-activated protein kinase-dependent and PI3K-dependent signaling pathways.

scholarly journals Glucose represses PPARαgene expression via AMP-activated protein kinase but not via p38 mitogen-activated protein kinase in the pancreatic β-cell

2009 ◽  
Vol 1 (4) ◽  
pp. 263-272 ◽  
Author(s):  
Erik JOLY ◽  
Raphaël RODUIT ◽  
Marie-Line PEYOT ◽  
Susan Amy HABINOWSKI ◽  
Neil Bertrand RUDERMAN ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Mitogen Activated Protein ◽  
Amp Activated Protein Kinase

scholarly journals Ghrelin exerts a proliferative effect on a rat pituitary somatotroph cell line via the mitogen-activated protein kinase pathway

2004 ◽  
pp. 233-240 ◽  
Author(s):  
AM Nanzer ◽  
S Khalaf ◽  
AM Mozid ◽  
RC Fowkes ◽  
MV Patel ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Protein Kinase ◽  
Cell Line ◽  
Kinase Inhibitor ◽  
Thymidine Incorporation ◽  
Mapk Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Gh3 Cells ◽  
Rat Pituitary ◽  
Mitogen Activated Protein

OBJECTIVES: Ghrelin is a brain-gut peptide with GH-releasing and appetite-inducing activities and a widespread tissue distribution. Ghrelin is the endogenous ligand of the GH secretagogue receptor type 1a (GHS-R1a), and both ghrelin and the GHS-R1a are expressed in the pituitary. There are conflicting data regarding the effects of ghrelin on cell proliferation. A positive effect on proliferation and activation of the mitogen-activated protein kinase (MAPK) pathway has been found in hepatoma, adipose, cardiomyocyte and prostate cell lines. However, ghrelin has also been shown to have anti-proliferative effects on breast, lung and thyroid cell lines. We therefore examined the effect of ghrelin on the rat pituitary cell line GH3. METHODS: RT-PCR was used for the detection of GHS-R1a and pre-proghrelin mRNA expression in GH3 cells. The effect of ghrelin on cell proliferation was studied using [(3)H]thymidine incorporation; cell counting and the activation of the MAPK pathway were studied using immunoblotting and inhibitors of the extracellular signal-regulated kinase 1 and 2 (ERK 1/2), protein kinase C (PKC) and tyrosine phosphatase pathways. RESULTS: GHS-R1a and ghrelin mRNA expression were detected in GH3 cells. Ghrelin, at 10(-10) to 10(-6) M concentrations, significantly increased [(3)H]thymidine incorporation (at 10(-9) M, 183+/-13% (means+/-s.e.m.) compared with untreated controls), while 12-phorbol 13-myristate acetate (PMA) at 10(-7) M (used as a positive control) caused a 212+/-14% increase. A reproducible stimulatory effect of desoctanoyl ghrelin was also observed on [(3)H]thymidine incorporation (135+/-5%; P<0.01 at 10(-9) M compared with control), as well as on the cell count (control 6.8 x 10(4)+/-8.7 x 10(3) cells/ml vs desoctanoyl ghrelin (10(-9) M) 1.04 x 10(5)+/-7.5 x 10(3) cells/ml; P<0.01). Ghrelin caused a significant increase in phosphorylated ERK 1/2 in immunoblotting, while desoctanoyl ghrelin showed a smaller but also significant stimulatory effect. The positive effect of ghrelin and desoctanoyl ghrelin on [(3)H]thymidine incorporation was abolished by the MAPK kinase inhibitor U0126, the PKC inhibitor GF109203X and the tyrosine kinase inhibitor tyrphostin 23, suggesting that the ghrelin-induced cell proliferation of GH3 cells is mediated both via a PKC-MAPK-dependent pathway and via a tyrosine kinase-dependent pathway. This could also be clearly demonstrated by Western blot analysis, where a transient increase in ERK 1/2 phosphorylation by ghrelin was attenuated by all three inhibitors. CONCLUSION: We have shown a novel role for ghrelin in stimulating the proliferation of a somatotroph pituitary tumour cell line, suggesting that ERK activation is involved in mediating the effects of ghrelin on cell proliferation. Desoctanoyl ghrelin showed a similar effect. As ghrelin has been shown to be expressed in both normal and adenomatous pituitary tissue, locally produced ghrelin may play a role in pituitary tumorigenesis via an autocrine/paracrine pathway.

Synergistic Activation of Mitogen-Activated Protein Kinase by Cyclic AMP and Myeloid Growth Factors Opposes Cyclic AMP’s Growth-Inhibitory Effects

Blood ◽  
1999 ◽  
Vol 93 (2) ◽  
pp. 537-553 ◽  
Author(s):  
Angel Wai-mun Lee
Keyword(s):  
Protein Kinase ◽  
Cyclic Amp ◽  
Cell Line ◽  
Mapk Pathway ◽  
Dominant Negative ◽  
Mitogen Activated Protein Kinase ◽  
Erk Activation ◽  
Mitogen Activated Protein ◽  
Erk Activity ◽  
Myeloid Progenitors

Abstract Colony-stimulating factors (CSFs) promote the proliferation, differentiation, commitment, and survival of myeloid progenitors, whereas cyclic AMP (cAMP)-mediated signals frequently induce their growth arrest and apoptosis. The ERK/mitogen-activated protein kinase (MAPK) pathway is a target for both CSFs and cAMP. We investigated how costimulation by cAMP and colony-stimulating factor-1 (CSF-1) or interleukin-3 (IL-3) modulates MAPK in the myeloid progenitor cell line, 32D. cAMP dramatically increased ERK activity in the presence of CSF-1 or IL-3. IL-3 also synergized with cAMP to activate ERK in another myeloid cell line, FDC-P1. The increase in ERK activity was transmitted to a downstream target, p90rsk. cAMP treatment of 32D cells transfected with oncogenic Ras was found to recapitulate the superactivation of ERK seen with cAMP and CSF-1 or IL-3. ERK activation in the presence of cAMP did not appear to involve any of the Raf isoforms and was blocked by expression of dominant-negative MEK1 or treatment with a MEK inhibitor, PD98059. Although cAMP had an overall inhibitory effect on CSF-1–mediated proliferation and survival, the inhibition was markedly increased if ERK activation was blocked by PD98059. These findings suggest that upregulation of the ERK pathway is one mechanism induced by CSF-1 and IL-3 to protect myeloid progenitors from the growth-suppressive and apoptosis-inducing effects of cAMP elevations.

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