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Attenuation of β‐cell death by P2Y 6 receptor agonist: A novel drug target for diabetes
Author(s) -
Balasubramanian Ramachandran,
Castro Sonia,
Maruoka Hirsohi,
Jacobson Kenneth A
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.769.8
Subject(s) - agonist , apoptosis , receptor , insulin , pharmacology , diabetes mellitus , context (archaeology) , chemistry , endocrinology , medicine , biology , biochemistry , paleontology
Apoptosis plays a key role in the reduction of β‐cell mass and has been proposed to mediate β‐cell reduction in type 1 and type 2 diabetes. Hence drugs which decrease blood glucose as well as protect β‐cells are required. In this context, we are evaluating the insulin secreting efficacy and cytoprotective nature of P2Y 6 receptor agonists in the present study. MIN6 cells grown to 80% confluency, were induced for insulin secretion in the presence of 16.7 mM glucose, with or without P2Y 6 agonists such as UDP, Up 3 U, and other novel P2Y 6 agonists. MIN6 cells were treated with 50 ng/ml TNF‐α for 24 h to induce apoptosis in the presence of P2Y 6 agonists. The efficacy of P2Y 6 agonist to attenuate apoptosis was determined by cell cycle analysis using flow cytometry. DNA fragmentation was detected by TUNEL assay based on 5‐bromo‐2’‐deoxyuridine(BrdU) labeling. Insulin secretion in MIN6 cells was significantly potentiated by P2Y 6 agonists. Also P2Y 6 agonists significantly mitigated TNF‐α induced cell death. These P2Y 6 agonists that are both insulin secretagogues and cytoprotective could be developed as a therapeutic intervention for diabetes mellitus. This work was supported by the Intramural Research Program of NIDDK, National Institutes of Health, MD, USA.