Studies on negative regulation of insulin gene expression in non-pancreatic cells

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Insulin gene is expressed only in pancreatic B cells. So we have examined the effect of the 5'-branking region of the human insulin gene on its expression in non-pancreatic cells. The presence of the region containing the insulin gene enhancer (-339 to -169 bp) markedly repressed the promoter activity of the insulin gene. This suppressive phenomenon was restored by the addition of forsholin or dibutyryl cAMP suggesting that this region alone is not sufficient to repress completely insulin gene expression in the presence of extracellular stimuli which increase the intracellular cAMP level. These results show negative regulation of human insulin gene expression in non-pancreatu cells by these regions.In order to clarify whether glucose transporter (GLUT) is glucosensor of pancreatic B cells, we have also studied GLUT. We isolated RNA from rat islets of Langerhans and confirmed the presence of GLUT2 mRNA and GLUT1 mRNA. And we also demonstrated glucose regulates GLUT2 mRNA expression. These results suggest GLUT2 may be glucosensor of pancreatic B cells.By using Zucker fatty and Wistar fatty rats as models of obesity and diabetes, we showed that GLUT2 mRNA levels increase in both model rats and suggest that increassed GLUT2 mRNA levels may be associated with the development of obesity