title: Glucose and other insulin secretagogues induce, rather than inhibit, expression of Id-1 and Id-3 in pancreatic islet beta cells.
abstract: OBJECTIVE
  Basic helix loop helix transcription factors regulate insulin gene transcription. Therefore, molecules that regulate their function should affect insulin production and secretion. As Id proteins inhibit basic helix loop helix function, it is important to determine whether they are expressed in beta cells and if insulin secretagogues regulate their expression.
  
  
  METHODS
  Human islets or insulinoma cells were cultured in different glucose concentrations or treated with secretagogues. Insulin secretion was measured using RIA. The Id mRNA and protein concentrations were measured using northern blots, RT-PCR, and western blots. Transfections of promoter-reporter constructs were used to estimate Id-1 gene transcription.
  
  
  RESULTS
  The Id-1 mRNA concentrations were twofold higher in islets cultured overnight in 10 mmol/l than in 2.5 mmol/l glucose. Addition of high glucose to islets previously cultured in low glucose, increased Id-1 mRNA concentrations within 30 min. Analyses using insulinoma cells revealed that Id-1 and Id-3 mRNA concentrations peaked 30 min after glucose was added, returned to near basal concentrations by 2 h and then progressively increased for 24 h. The Id-1 protein concentrations changed in a similar pattern. Insulin secretagogues that act through different signaling pathways also induced Id expression. The Id response required glucose metabolism, calcium, and RNA synthesis but not protein synthesis. Glucose-responsive elements are confined to the 5'-region of the Id-1 gene.
  
  
  CONCLUSIONS
  The concomitant induction of Id-1 and Id-3 expression, insulin gene transcription, and insulin secretion suggests that physiological concentrations of Ids do not inhibit insulin gene transcription and Ids could play unexpected and novel roles in promoting beta-cell function.
authors.affiliation: Department of Internal Medicine, Division of Metabolism, Washington University School of Medicine, 660 South Euclid Avenue, Saint Louis, Missouri 63110, USA.
authors.forename: B M
authors.initials: BM
authors.lastname: Wice
authors.forename: E
authors.initials: E
authors.lastname: Bernal-Mizrachi
authors.forename: M A
authors.initials: MA
authors.lastname: Permutt
mesh_terms: D016475:3T3 Cells; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects*; D005947:Glucose / Q000494:pharmacology*; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1; D051796:Inhibitor of Differentiation Proteins; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007340:Insulinoma / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D009363:Neoplasm Proteins; D010190:Pancreatic Neoplasms / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D004268:DNA-Binding Proteins; C497453:ID1 protein, human; C497455:Idb1 protein, mouse; D051798:Inhibitor of Differentiation Protein 1; D051796:Inhibitor of Differentiation Proteins; D007328:Insulin; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors; C075640:ID3 protein, human; D005947:Glucose