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Activation of distinct P2Y receptor subtypes stimulates insulin secretion in MIN6 mouse pancreatic beta cells

Ramachandran Balasubramanian1, Inigo Ruiz de Azua, Jürgen Wess

  • 1Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bldg. 8A, Rm. B1A-19, Bethesda, MD, USA.

Biochemical Pharmacology
|January 14, 2010
PubMed

Insights

Extracellular nucleotides acting on P2Y(1) and P2Y(6) receptors in pancreatic beta cells enhance insulin secretion. Certain P2Y receptor agonists also protect cells from apoptosis, suggesting therapeutic potential for diabetes treatment.

Area of Science:

  • Endocrinology and Metabolism
  • Cell Biology
  • Pharmacology

Background:

  • Extracellular nucleotides and purinergic receptors are implicated in various diseases, including diabetes.
  • Pancreatic beta cells express purinergic receptors, but their role in insulin secretion is debated.
  • Understanding purinergic signaling is crucial for developing novel diabetes therapies.

Purpose of the Study:

  • To investigate the role of P2Y(1) and P2Y(6) receptors in regulating insulin secretion and cell death in mouse pancreatic beta cells (MIN6).
  • To assess the potential of selective P2Y receptor agonists as therapeutic agents for diabetes.

Main Methods:

  • Reverse transcription-polymerase chain reaction (RT-PCR) to confirm P2Y(1) and P2Y(6) receptor expression.
  • Stimulation of MIN6 cells with glucose and specific P2Y(1) and P2Y(6) receptor agonists (2-MeSADP and Up(3)U).
  • Flow cytometry to evaluate P2Y agonist effects on tumor necrosis factor-alpha (TNF-alpha)-induced apoptosis.

Main Results:

  • Both P2Y(1) and P2Y(6) receptor agonists significantly increased insulin secretion in MIN6 cells.
  • Agonist-induced insulin secretion was blocked by selective antagonists MRS2179 (P2Y(1)) and MRS2578 (P2Y(6)).
  • The P2Y(6) agonist Up(3)U, but not the P2Y(1) agonist 2-MeSADP, protected MIN6 cells against TNF-alpha-induced apoptosis.

Conclusions:

  • Selective activation of P2Y(1) and P2Y(6) receptors enhances insulin secretion in pancreatic beta cells.
  • P2Y(6) receptor stimulation confers protection against apoptosis, indicating a dual role in beta cell function.
  • P2Y receptor ligands show promise for the therapeutic management of diabetes.

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