Phorbol esters showing selective activation of PKS isozymes in vitro regulate thyroid function and insulin-like growth factor binding protein secretion

1994 ◽  
Vol 6 (4) ◽  
pp. 439-448 ◽  
Author(s):  
Margaret C. Eggo ◽  
Michael C. Sheppard ◽  
Fred J. Evans ◽  
Janet M. Lord
Keyword(s):  
Growth Factor ◽  
Thyroid Function ◽  
Protein Secretion ◽  
Phorbol Esters ◽  
Binding Protein ◽  
Insulin Like Growth Factor ◽  
Selective Activation ◽  
Factor Binding

Antagonistic effects of phorbol esters on insulin regulation of insulin-like growth factor-binding protein-1 (IGFBP-1) but not glucose-6-phosphatase gene expression

2001 ◽  
Vol 359 (3) ◽  
pp. 611-619 ◽  
Author(s):  
Satish PATEL ◽  
Pamela A. LOCHHEAD ◽  
Graham RENA ◽  
Calum SUTHERLAND
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Map Kinases ◽  
Phorbol Esters ◽  
Binding Protein ◽  
Gene Promoter ◽  
Dependent Manner ◽  
Insulin Like Growth Factor ◽  
Factor Binding

Glucose-6-phosphatase (G6Pase) and insulin-like growth factor-binding protein-1 (IGFBP-1) genes contain a homologous promoter sequence that is required for gene repression by insulin. Interestingly, this element interacts with members of the forkhead family of transcription factors [e.g. HNF3 (hepatic nuclear factor 3), FKHR (forkhead in rhabdomyosarcoma)] in vitro, while insulin promotes the phosphorylation and inactivation of FKHR in a phosphatidylinositol 3-kinase- and protein kinase B (PKB)-dependent manner. This mechanism has been proposed to underlie insulin action on G6Pase and IGFBP-1 gene transcription. However, we find that treatment of cells with phorbol esters mimics the effect of insulin on G6Pase, but not IGFBP-1, gene expression. Indeed, phorbol ester treatment actually blocks the ability of insulin to repress IGFBP-1 gene expression. In addition, the action of phorbol esters is significantly reduced by inhibition of the p42/p44 mitogen-activated protein (MAP) kinase pathway. However insulin-induced phosphorylation of PKB or FKHR is not affected by the presence of phorbol esters. Therefore we suggest that activation of p42/p44 MAP kinases will reduce the sensitivity of the IGFBP-1 gene promoter, but not the G6Pase gene promoter, to insulin. Importantly, the activation of PKB and phosphorylation of FKHR is not, in itself, sufficient to reduce IGFBP-1 gene expression in the presence of phorbol esters.

INSULIN AND VARIATION IN GLUCOSE LEVELS MODIFY THE SECRETION RATES OF THE GROWTH HORMONE-INDEPENDENT INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN-1 IN THE HUMAN HEPATOBLASTOMA CELL LINE HEP G2

1989 ◽  
Vol 123 (3) ◽  
pp. R17-R20 ◽  
Author(s):  
A.M. Cotterill ◽  
C.T. Cowell ◽  
M. Silink
Keyword(s):  
Growth Factor ◽  
Cell Line ◽  
Glucose Concentration ◽  
Binding Protein ◽  
Suitable Model ◽  
Insulin Like Growth Factor ◽  
Hep G2 ◽  
Factor Binding ◽  
Glucose Levels

ABSTRACT The plasma level of the GH-independent insulin-like growth factor binding-protein-1 (IGFBP-1) is regulated inversely by insulin. In this study the effect of insulin and changes in the glucose concentration on in-vitro IGFBP-1 secretion by the Hep G2 cell line was studied. Media from confluent cells in 12 replicates were collected for consecutive periods: initial control (20 h), study(6 h) and recovery (20 h). Insulin suppressed IGFBP-1 secretion maximally at 100 mU/1 (−32%) within 6 h. The secretion of IGFBP-1 was stimulated by a decrease in the glucose concentration in the medium, maximally (+25%) with a decrease from 24 to 6 mmol/l. Stimulation by varying glucose levels and suppression by insulin of IGFBP-1 secretion persisted on return to control conditions after the removal of physiological concentrations of glucose (4 - 12 mmol/l) and insulin (50 - 500 mU/1). The findings in the Hep G2 cell line that a variation in the physiological concentrations of glucose and insulin each independently regulate IGFBP-1 secretion suggest that this cell line may by a suitable model for further in-vitro studies of the regulation of secretion of IGFBP-1.

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