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Regulation of pancreatic β-cell function and mass dynamics by prostaglandin signaling

Journal of Cell Communication and Signaling volume 11, pages 105–116 (2017)Cite this article

Abstract

Prostaglandins (PGs) are signaling lipids derived from arachidonic acid (AA), which is metabolized by cyclooxygenase (COX)-1 or 2 and class-specific synthases to generate PGD2, PGE2, PGF2α, PGI2 (prostacyclin), and thromboxane A2. PGs signal through G-protein coupled receptors (GPCRs) and are important modulators of an array of physiological functions, including systemic inflammation and insulin secretion from pancreatic islets. The role of PGs in β-cell function has been an active area of interest, beginning in the 1970s. Early studies demonstrated that PGE2 inhibits glucose-stimulated insulin secretion (GSIS), although more recent studies have questioned this inhibitory action of PGE2. The PGE2 receptor EP3 and one of the G-proteins that couples to EP3, GαZ, have been identified as negative regulators of β-cell proliferation and survival. Conversely, PGI2 and its receptor, IP, play a positive role in the β-cell by enhancing GSIS and preserving β-cell mass in response to the β-cell toxin streptozotocin (STZ). In comparison to PGE2 and PGI2, little is known about the function of the remaining PGs within islets. In this review, we discuss the roles of PGs, particularly PGE2 and PGI2, PG receptors, and downstream signaling events that alter β-cell function and regulation of β-cell mass.

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Abbreviations

AA:

Arachidonic Acid

COX:

cyclooxygenase

Epac2:

Exchange Protein Directly Activated by cAMP 2

GPCR:

G-Protein Coupled Receptor

GLP-1:

Glucagon-Like Peptide-1

HFD:

High Fat Diet

IL-1β:

Interleukin 1-β

ITT:

Insulin Tolerance Test

IP-GTT:

Intraperitoneal Glucose Tolerance Test

JNK:

c-Jun N-Terminal Kinase

mPGES-1:

microsomal PGE2 Synthase 1

NSAIDs:

Non-Steroidal Anti-Inflammatory Drugs

NFκB:

Nuclear Factor κB

Pdx1:

Pancreatic and duodenal homeobox 1

PTx:

Pertussis Toxin

PI3K:

Phosphatidylinositol 3-Kinase

PLA2 :

Phospholipase A2

PG:

Prostaglandin

PKA:

Protein Kinase A

SNP:

Single Nucleotide Polymorphism

STZ:

Streptozotocin

T2D:

Type 2 Diabetes

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Acknowledgments

We would like to thank members of the Gannon lab for helpful discussions and, in particular, Dr. Raymond Pasek for critical reading of the manuscript. We also thank Dr. R. Paul Robertson for reading and helpful discussions of the manuscript. This work was supported by a Merit Award from the Veterans Administration (Grant 1 I01 BX003744-01) to M.G.

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Affiliations

  1. Department of Veterans Affairs, Tennessee Valley Health Authority, Nashville, TN, USA

    Bethany A. Carboneau, Richard M. Breyer & Maureen Gannon

  2. Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA

    Bethany A. Carboneau & Maureen Gannon

  3. Program in Developmental Biology, Vanderbilt University, Nashville, TN, USA

    Bethany A. Carboneau & Maureen Gannon

  4. Department of Medicine, Division of Nephrology, Vanderbilt University Medical Center, Nashville, USA

    Richard M. Breyer

  5. Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA

    Maureen Gannon

  6. Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Vanderbilt University Medical Center, Nashville, TN, USA

    Maureen Gannon

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  1. Bethany A. Carboneau
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Correspondence to Maureen Gannon.

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Carboneau, B.A., Breyer, R.M. & Gannon, M. Regulation of pancreatic β-cell function and mass dynamics by prostaglandin signaling. J. Cell Commun. Signal. 11, 105–116 (2017). https://doi.org/10.1007/s12079-017-0377-7

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Keywords

  • β-cell
  • GSIS
  • Proliferation
  • Prostaglandins