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Molecular Basis of cAMP Signaling in Pancreatic β Cells

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Islets of Langerhans

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 cAMP-regulated 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.

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Acknowledgments

This work was supported by American Diabetes Association Basic Science Awards to GGH (7-12-BS-077) and CAL (1-12-BS-109). National Institutes of Health funding was provided to GGH (DK069575) and MAH (DK090245, DK090816, DK084949, DK079637). GGH and OGC acknowledge the support of SUNY Upstate Medical University.

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  1. Departments of Medicine and Pharmacology, SUNY Upstate Medical University, 505 Irving Avenue, IHP 4310, Syracuse, NY, 13210, USA

    George G. Holz

  2. Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Woo-Jin Song

  3. Department of Medicine, SUNY Upstate Medical University, Syracuse, NY, USA

    Oleg G. Chepurny & Colin A. Leech

  4. Departments of Pediatrics, Medicine, and Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Mehboob A. Hussain

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  1. George G. Holz
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  2. Oleg G. Chepurny
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  4. Woo-Jin Song
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  5. Mehboob A. Hussain
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Correspondence to George G. Holz .

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  1. Department of Clinical Sciences and Education, Sodersjukhuset, Karolinska Institutet, Stockholm, Sweden

    Md. Shahidul Islam

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Holz, G.G., Chepurny, O.G., Leech, C.A., Song, WJ., Hussain, M.A. (2015). Molecular Basis of cAMP Signaling in Pancreatic β Cells. In: Islam, M. (eds) Islets of Langerhans. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6686-0_25

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