The reduction of insulin gene transcription in HIT-T15 beta cells chronically exposed to high glucose concentration is associated with the loss of RIPE3b1 and STF-1 transcription factor expression.

Sharma A, Olson LK, Robertson RP, Stein R
Mol Endocrinol. 1995 9 (9): 1127-34

PMID: 7491105 · DOI:10.1210/mend.9.9.7491105

The most important regulator of insulin gene expression in pancreatic beta- cells is glucose, which affects gene transcription, mRNA translation, and secretion. Insulin gene transcription is both positively and negatively regulated by glucose. Recently, we have shown that the inhibition of insulin gene transcription caused by passaging HIT T-15 beta-cells, in the presence of high glucose, was due, in part, to reduced expression of a key regulator of insulin enhancer-mediated expression, somatostatin transcription factor-1 (STF-1). In this study, we have examined whether the activity of the other essential transcription regulators of insulin gene expression, the RIPE3b1 and insulin control element (ICE) activators, were also influenced in these HIT T-15 cells. The results show that the binding and trans-activation functions of the RIPE3b1 activator are reduced in parallel with the loss in STF-1 and insulin gene expression. In contrast, the regulatory properties of the ICE activator are unaffected. Our studies indicate that insulin gene transcription is inhibited by glucose through a mechanism involving reduced expression of both the RIPE3b1 and STF-1 activators in HIT T-15 cells but is independent of the ICE activator.

MeSH Terms (19)

Animals Base Sequence Cell Line Gene Expression Regulation Genes, Homeobox Genes, Reporter Glucose Homeodomain Proteins Insulin Islets of Langerhans Luciferases Molecular Sequence Data Rats Recombinant Fusion Proteins Regulatory Sequences, Nucleic Acid Trans-Activators Transcription, Genetic Transcription Factors Transfection

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