Modulation of growth-related gene expression and growth inhibition by cyclic adenosine 3',5'-monophosphate-elevating agents in the insulin-producing cell line beta TC1.

Abstract:

:We studied the involvement of the cAMP pathway in the regulation of beta TC1 cell growth with the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) and the activator of adenylate cyclase forskolin. We examined the effect of the increase in cAMP content on the serum-induced resumption of the cell cycle of quiescent cells. IBMX and forskolin both inhibited the mitogenic effect of serum in a concentration-dependent manner. Intracellular cAMP levels were, respectively, enhanced 3.0- and 8.6-fold by IBMX (0.5 mM) and forskolin (20 microM) within 1 h. IBMX and forskolin were also inducers of insulin release, indicating that the growth-arrested beta TC1 cells have retained the essential characteristics of the normal differentiated beta-cells. The effects of IBMX and forskolin were correlated with a modulation of cell cycle-related gene expression. IBMX induced expression of the c-fos gene, which was further enhanced by the simultaneous addition of serum, whereas forskolin alone elicited maximal induction of this gene. Interestingly, c-jun expression was only enhanced with forskolin. We also studied the effects of IBMX and forskolin on the expression of the simian virus-40 T-antigen controlled by the rat insulin II promoter in beta TC1 cells. IBMX and forskolin inhibited the serum-induced accumulation of simian virus-40 T-antigen mRNA in quiescent as well as exponentially growing beta TC1 cells.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Lavergne C,Breant B,Rosselin G

doi

10.1210/endo.131.5.1385100

subject

Has Abstract

pub_date

1992-11-01 00:00:00

pages

2351-6

issue

5

eissn

0013-7227

issn

1945-7170

journal_volume

131

pub_type

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