Reduction of insulin gene transcription in HIT-T15 beta cells chronically exposed to a supraphysiologic glucose concentration is associated with loss of STF-1 transcription factor expression

摘要: Abstract Chronic exposure of HIT-T15 beta cells to elevated glucose concentrations leads decreased insulin gene transcription. The reduction in expression is accompanied by diminished binding a glucose-sensitive transcription factor (termed GSTF) that interacts with two (A+T)-rich elements within the 5' flanking control region gene. In this study we examined whether GSTF corresponds recently cloned STF-1, homeodomain protein whose restricted nucleus endodermal duodenum and pancreas. We found an affinity-purified antibody recognizing STF-1 supershifted activator complex formed from extracts. addition, demonstrated mRNA levels closely correlated change chronically cultured under supraphysiologic concentrations. these could be accounted for rate transcription, suggesting posttranscriptional mechanism. support hypothesis, no accumulated passaged 11.1 mM glucose. only RNA species detected was 6.4-kb hybridized 3' STF-1-specific cDNA probes. suggest represents precursor splicing defective cells. Overall, suggests reduced key transcriptional regulatory factor, contributes decrease concentration.