Paradoxical regulation of Sp1 transcription factor by glucagon.

Abstract:

:Insulin is a potent regulator of Sp1 transcription factor. To examine if glucagon, which usually antagonizes insulin, regulates Sp1, we assessed the levels of Sp1 by Western blotting from H-411E cells exposed to glucagon with or without insulin. Glucagon alone (1.5 x 10(-9) to 1.5 x 10(-5) M) stimulated Sp1 accumulation but inhibited insulin's (10,000 microU/ml) stimulatory effect on Sp1. We also assessed the effect of TNF-alpha, wortmannin, a PI3K inhibitor, and cAMP-dependent protein kinase inhibitor on Sp1 accumulation. While TNF-alpha (5 ng/ml) blocked insulin-stimulated Sp1, it failed to block stimulation of Sp1 by glucagon (1.5 x 10(-5) M). Similarly, wortmannin inhibited insulin- but not glucagon-stimulated Sp1, whereas protein kinase inhibitor had an opposite effect. Thus, insulin acts primarily via PI3K, and glucagon apparently stimulates through a cAMP-dependent pathway. Insulin increased the staining intensity of Sp1 seen exclusively in the nuclei of H-411E cells. Sp1 was demonstrable in both nucleus and cytoplasm after glucagon treatment. Finally, as judged by immunoblotting to specific antibody, insulin but not glucagon, stimulated O-glycosylation of Sp1. Thus, unique signaling mechanisms mediate the response of Sp1 to glucagon in the presence or absence of insulin.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Keembiyehetty CN,Candelaria RP,Majumdar G,Raghow R,Martinez-Hernandez A,Solomon SS

doi

10.1210/endo.143.4.8756

subject

Has Abstract

pub_date

2002-04-01 00:00:00

pages

1512-20

issue

4

eissn

0013-7227

issn

1945-7170

journal_volume

143

pub_type

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