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Diabetes Obes Metab. 2013 Sep;15 Suppl 3:176-84. doi: 10.1111/dom.12158.

Small-molecule inhibition of inflammatory β-cell death.

Author information

1
Chemical Biology Program, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.

Abstract

With the worldwide increase in diabetes prevalence there is a pressing unmet need for novel antidiabetic therapies. Insufficient insulin production due to impaired β-cell function and apoptotic reduction of β-cell mass is a common denominator in the pathogenesis of diabetes. Current treatments are directed at improving insulin sensitivity, and stimulating insulin secretion or replacing the hormone, but do not target progressive apoptotic β-cell loss. Here we review the current development of small-molecule inhibitors designed to rescue β-cells from apoptosis. Several distinct classes of small molecules have been identified that protect β-cells from inflammatory, oxidative and/or metabolically induced apoptosis. Although none of these have yet reached the clinic, β-cell protective small molecules alone or in combination with current therapies provide exciting opportunities for the development of novel treatments for diabetes.

KEYWORDS:

apoptosis; glucolipotoxicity; glucotoxicity; inflammation; lipotoxicity; proinflammatory cytokines; small-molecules; β-cell

PMID:
24003935
PMCID:
PMC3777666
DOI:
10.1111/dom.12158
[Indexed for MEDLINE]
Free PMC Article
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