Journal of Cell Communication and Signaling

, Volume 11, Issue 2, pp 105–116 | Cite as

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

  • Bethany A. Carboneau
  • Richard M. Breyer
  • Maureen Gannon
Review

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, PGF, 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.

Keywords

β-cell GSIS Proliferation Prostaglandins 

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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Copyright information

© The International CCN Society (outside the USA) 2017

Authors and Affiliations

  • Bethany A. Carboneau
    • 1
    • 2
    • 3
  • Richard M. Breyer
    • 1
    • 4
  • Maureen Gannon
    • 1
    • 2
    • 3
    • 5
    • 6
  1. 1.Department of Veterans Affairs, Tennessee Valley Health AuthorityNashvilleUSA
  2. 2.Department of Molecular Physiology and BiophysicsVanderbilt UniversityNashvilleUSA
  3. 3.Program in Developmental BiologyVanderbilt UniversityNashvilleUSA
  4. 4.Department of Medicine, Division of NephrologyVanderbilt University Medical CenterNashvilleUSA
  5. 5.Department of Cell and Developmental BiologyVanderbilt UniversityNashvilleUSA
  6. 6.Department of Medicine, Division of Diabetes, Endocrinology and MetabolismVanderbilt University Medical CenterNashvilleUSA

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