Glucose and other insulin secretagogues induce, rather than inhibit, expression of Id-1 and Id-3 in pancreatic islet beta cells

B. M. Wice, E. Bernal-Mizrachi, M. A. Permutt

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Aims/hypothesis. 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 two-fold 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. Conclusion/interpretation. 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.

Original languageEnglish (US)
Pages (from-to)453-463
Number of pages11
JournalDiabetologia
Volume44
Issue number4
DOIs
StatePublished - Apr 30 2001
Externally publishedYes

Keywords

  • Basic helix loop helix
  • Beta cell
  • Helix loop helix
  • Id-1
  • Id-2
  • Id-3
  • Insulin gene transcription
  • Insulin secretion

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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