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 language | English (US) |
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Title of host publication | Islets of Langerhans, Second Edition |
Publisher | Springer Netherlands |
Pages | 565-603 |
Number of pages | 39 |
ISBN (Electronic) | 9789400766860 |
ISBN (Print) | 9789400766853 |
DOIs | |
State | Published - Jan 1 2015 |
Keywords
- Cyclic amp
- Diabetes
- Epac2
- Glp-1
- Protein kinase a
ASJC Scopus subject areas
- General Medicine
- General Biochemistry, Genetics and Molecular Biology
- General Chemistry