Heit Jeremy J
Department of Developmental Biology, B300 Beckman Center for Molecular and Genetic Medicine, Stanford University School of Medicine, 279 Campus Drive, Stanford, CA 94305-5329, USA.
Bioessays. 2007 Oct;29(10):1011-21. doi: 10.1002/bies.20644.
Pancreatic beta-cells in the islet of Langerhans produce the hormone insulin, which maintains blood glucose homeostasis. Perturbations in beta-cell function may lead to impairment of insulin production and secretion and the onset of diabetes mellitus. Several essential beta-cell factors have been identified that are required for normal beta-cell function, including six genes that when mutated give rise to inherited forms of diabetes known as Maturity Onset Diabetes of the Young (MODY). However, the intracellular signaling pathways that control expression of MODY and other factors continue to be revealed. Post-transplant diabetes mellitus in patients taking the calcineurin inhibitors tacrolimus (FK506) or cyclosporin A indicates that calcineurin and its substrate the Nuclear Factor of Activated T-cells (NFAT) may be required for beta-cell function. Here recent advances in our understanding of calcineurin and NFAT signaling in the beta-cell are reviewed. Novel therapeutic approaches for the treatment of diabetes are also discussed.
胰岛中的胰腺β细胞产生激素胰岛素，以维持血糖稳态。β细胞功能的紊乱可能导致胰岛素产生和分泌受损以及糖尿病的发生。已经确定了几种正常β细胞功能所需的重要β细胞因子，包括六个基因，这些基因发生突变时会引发遗传性糖尿病，即青年发病的成年型糖尿病（MODY）。然而，控制MODY和其他因子表达的细胞内信号通路仍在不断被揭示。服用钙调神经磷酸酶抑制剂他克莫司（FK506）或环孢素A的患者发生移植后糖尿病，这表明钙调神经磷酸酶及其底物活化T细胞核因子（NFAT）可能是β细胞功能所必需的。本文综述了我们对β细胞中钙调神经磷酸酶和NFAT信号传导的最新认识。还讨论了治疗糖尿病的新治疗方法。
