Molecular basis of cAMP signaling in pancreatic β cells

George G. Holz, Oleg G. Chepurny, Colin A. Leech, Woo Jin Song, Mehboob A. Hussain

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Recent advances in conditional gene targeting and cyclic nucleotide research further our understanding of how the incretin hormone GLP-1 exerts a therapeutically important action to restore pancreatic insulin secretion in patients with type 2 diabetes mellitus (T2DM). These studies demonstrate that the pancreatic β-cell GLP-1 receptor has the capacity to signal through two distinct branches of the adenosine 3′,5′-cyclic monophosphate (cAMP) signal transduction network; one branch activates protein kinase A (PKA), and the second engages a cAMPregulated guanine nucleotide exchange factor designated as Epac2. Under normal dietary conditions, specific activation of the cAMP-PKA branch in mice dramatically augments glucose-stimulated insulin secretion (GSIS). However, under conditions of diet-induced insulin resistance, cAMP-Epac2 signaling in the control of GSIS becomes prominent. This chapter provides an update on GLP-1 receptor signaling in the islets of Langerhans, with special emphasis on key molecular events that confer “plasticity” in the β-cell cAMP signal transduction network. The reader is reminded that an excellent review of β-cell cAMP signaling can also be found in the prior first edition of this book.

Original languageEnglish (US)
Title of host publicationIslets of Langerhans, Second Edition
PublisherSpringer Netherlands
Pages565-603
Number of pages39
ISBN (Electronic)9789400766860
ISBN (Print)9789400766853
DOIs
StatePublished - Jan 1 2015

Keywords

  • Cyclic amp
  • Diabetes
  • Epac2
  • Glp-1
  • Protein kinase a

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)

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  • Cite this

    Holz, G. G., Chepurny, O. G., Leech, C. A., Song, W. J., & Hussain, M. A. (2015). Molecular basis of cAMP signaling in pancreatic β cells. In Islets of Langerhans, Second Edition (pp. 565-603). Springer Netherlands. https://doi.org/10.1007/978-94-007-6686-0_25