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Glucotoxicity‐induced apoptosis and suppression of cell proliferation in pancreatic beta‐cells
Author(s) -
Han Diana,
Yang Byungho,
Claycombe Kate J.,
Yu SeongWoon,
Kim EunKyoung
Publication year - 2008
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.22.1_supplement.1095.2
Subject(s) - beta cell , apoptosis , endocrinology , medicine , cell growth , programmed cell death , dna fragmentation , diabetes mellitus , pancreas , cell , insulin , secretion , beta (programming language) , fragmentation (computing) , chemistry , microbiology and biotechnology , biology , islet , biochemistry , ecology , computer science , programming language
Diabetes is associated with an increased risk for a number of serious, sometimes life‐threatening complications. It is a loss of beta‐cell function and/or mass that eventually defines the disease. Glucose, the main regulator of insulin secretion and production, exerts negative effects on beta‐cell function when present in excessive amounts over a prolonged period. This chronic hyperglycemia is detrimental to pancreatic beta‐cells, causing impaired insulin secretion and playing an essential role in the regulation of beta‐cell turnover through a poorly known process, glucose toxicity (glucotoxicity). Our studies demonstrate that chronic exposure of hyperglycemia (30 mM glucose) to INS‐1 pancreatic beta‐cells causes an apoptotic programmed cell death, which coincides with induction of caspase‐3 activation and DNA fragmentation, but without a change in Bcl‐2 and Bcl‐xL protein levels. Our results also indicate that pancreatic beta‐cells undergo a reduced proliferation mediated by decreased p70S6K activation following hyperglycemia. Accordingly, our studies suggest that hyperglycemia induces caspase‐dependent pancreatic cell apoptosis and suppress cell proliferation, thereby leading to a reduction in cell viability.