The role of the insulin control element and RIPE3b1 activators in glucose-stimulated transcription of the insulin gene.

Sharma A, Fusco-DeMane D, Henderson E, Efrat S, Stein R
Mol Endocrinol. 1995 9 (11): 1468-76

PMID: 8584024 · DOI:10.1210/mend.9.11.8584024

The most important regulator of insulin expression in islet beta-cells is glucose, which stimulates insulin gene transcription, protein synthesis, and secretion. Glucose-induced insulin gene transcription is regulated by cis-acting elements found within the 5'-flanking region of the insulin gene. We previously demonstrated that the insulin control element (ICE, -100 to -91) and RIPE3b1 (-115 to -107) elements mediated this response in the HIT T-15 beta-cell line. In this study, we examined more closely how these insulin gene control elements regulate glucose-induced transcription. RIPE3b1 element binding was shown to be induced by glucose in both mouse beta TC-6 and beta TC-3 cell lines, although higher glucose concentrations were necessary in the beta-cells (beta TC-6) that responded to physiological glucose concentrations. RIPE3b1 binding was also regulated in glucose-stimulated beta- cells by various effectors of this response. The RIPE3b1 or ICE elements were shown to independently direct glucose-stimulated expression from minimal heterologous promoter constructs. We conclude that the RIPE3b1 and ICE elements are the principal mediators of glucose-stimulated transcription of the insulin gene.

MeSH Terms (16)

Animals Antigens, Polyomavirus Transforming Base Sequence Gene Expression Regulation, Neoplastic Glucose Insulin Insulinoma Mice Mice, Transgenic Molecular Sequence Data Pancreatic Neoplasms Recombinant Fusion Proteins Regulatory Sequences, Nucleic Acid RNA, Messenger Transcription, Genetic Tumor Cells, Cultured

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