title: Small-molecule inhibition of inflammatory β-cell death.
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.
authors.affiliation: Chemical Biology Program, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
authors.forename: M
authors.initials: M
authors.lastname: Lundh
authors.forename: S S
authors.initials: SS
authors.lastname: Scully
authors.forename: T
authors.initials: T
authors.lastname: Mandrup-Poulsen
authors.forename: B K
authors.initials: BK
authors.lastname: Wagner
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007249:Inflammation / Q000517:prevention & control*; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000502:physiology*; D054852:Small Molecule Libraries / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D007004:Hypoglycemic Agents; D054852:Small Molecule Libraries
keywords: apoptosis; glucolipotoxicity; glucotoxicity; inflammation; lipotoxicity; proinflammatory cytokines; small-molecules; β-cell