Glucose and forskolin regulate IAPP gene expression through different signal transduction pathways

Wei Qun Ding, Eileen Holicky, Laurence J. Miller

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Molecular mechanisms for the regulation of islet amyloid polypeptide (IAPP) gene expression remain unclear. In the present study, we investigated the effects of glucose and forskolin on IAPP gene regulation in the INS-1 islet β-cell line. Both glucose and forskolin increased the level of expression of this gene, as measured by Northern blot analysis, and increased IAPP gene transcription in a time- and concentration-dependent manner, as demonstrated in a reporter gene assay. Although inhibition of protein kinase A activity with H-89 eliminated the effect of forskolin on this gene, the glucose effect was unaffected. This supported the predominant use of a protein kinase A-independent signaling pathway for glucose regulation of the IAPP gene. Electrophoretic mobility shift assay further indicated that glucose and forskolin regulated expression of this gene by targeting different elements of the promoter. Mutation of the cAMP regulatory element flanking the IAPP coding region resulted in the loss of most of the forskolin-stimulated IAPP gene promoter activity, whereas glucose-enhanced IAPP gene transcription was unaffected. These results demonstrate parallel and distinct regulatory pathways involved in glucose- and forskolin-induced IAPP gene expression in this model β-cell system.

Original languageEnglish (US)
Pages (from-to)E938-E945
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume281
Issue number5 44-5
StatePublished - Dec 19 2001

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Keywords

  • Cyclic adenosine 3,5-monophosphate
  • Islet amyloid polypeptide
  • Protein kinase A

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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