The role of the insulin control element and RIPE3b1 activators in glucose-stimulated transcription of the insulin gene.
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.
Sharma
A
A
Department of Molecular Physiology and Biophysics, Vanderbilt Medical Center, Nashville, Tennessee 37232, USA.
Fusco-DeMane
D
D
Henderson
E
E
Efrat
S
S
Stein
R
R
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000096:biosynthesis / Q000235:genetics; D001483:Base Sequence; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000096:biosynthesis / Q000235:genetics*; D007340:Insulinoma / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010190:Pancreatic Neoplasms / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012045:Regulatory Sequences, Nucleic Acid; D014158:Transcription, Genetic / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D000952:Antigens, Polyomavirus Transforming; D007328:Insulin; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D005947:Glucose