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DNA Cell Biol. 1999 Jun;18(6):471-9.

Regulation of the insulin gene by glucose: stimulation of trans-activation potency of human PDX-1 N-terminal domain.

Author information

1
Department of Endocrinology & Metabolism, Hebrew University, Hadassah Medical Center, Jerusalem, Israel.

Abstract

The beta cells in pancreatic islets of Langerhans increase insulin gene transcription in response to glucose. The pancreatic and duodenal homeobox-1 (PDX-1) plays a major role in glucose-induced insulin transcription. We studied the functional regions of the human PDX-1 protein fused to the DNA-binding domain of the transcription factor Gal4. The results indicate that the N-terminal domain of the hPDX-1, required for transactivation (amino acids 1-120) in transfected betaTC6 and HeLa cells, is also regulated by extracellular glucose concentrations in transfected rat islets. Deletion analyses have led to the mapping of two regions within the N terminus that are essential for its trans-activation properties. One sequence spans amino acids 97-120 in transfected islet and HeLa cells or amino acids 77-120 in betaTC6 cells; the other includes the highly conserved B box (amino acids 31-41). We thus present evidence of a glucose effect on hPDX-1 trans-activation activity, in addition to the previously described regulatory effect on its DNA-binding activity.

PMID:
10390156
DOI:
10.1089/104454999315196
[Indexed for MEDLINE]

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