TY - JOUR
T1 - The reduction of insulin gene transcription in HIT-T15 β cells chronically exposed to high glucose concentration is associated with the loss of RIPE3b1 and STF-1 transcription factor expression
AU - Sharma, A.
AU - Olson, L. K.
AU - Robertson, R. P.
AU - Stein, R.
PY - 1995/9
Y1 - 1995/9
N2 - The most important regulator of insulin gene expression in pancreatic β- 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 β-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.
AB - The most important regulator of insulin gene expression in pancreatic β- 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 β-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.
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U2 - 10.1210/me.9.9.1127
DO - 10.1210/me.9.9.1127
M3 - Article
C2 - 7491105
AN - SCOPUS:0029086781
SN - 0888-8809
VL - 9
SP - 1127
EP - 1134
JO - Molecular Endocrinology
JF - Molecular Endocrinology
IS - 9
ER -