Mizukami Hiroki, Wada Ryuichi, Koyama Motoi, Takeo Teruko, Suga Sechiko, Wakui Makoto, Yagihashi Soroku
Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.
Virchows Arch. 2008 Apr;452(4):383-92. doi: 10.1007/s00428-007-0508-2. Epub 2008 Jan 31.
Progressive decline of islet beta cell mass is a hallmark of type 2 diabetes, where nutritional insults are invoked in the pathologic process. Its detailed mechanisms are, however, incompletely understood. We explored the effect of sucrose diet on mitochondria in Goto Kakizaki (GK) rats, a spontaneously diabetic model. Six-week-old male GK rats were given 30% sucrose orally for 2 weeks. Normal Wistar rats fed with sucrose served as controls. Compared to untreated GK rats, sucrose-fed GK rats showed severe degeneration and death of beta cells with disrupted and swollen mitochondria and a greater beta cell loss. Submicroscopic analysis disclosed a smaller mean volume and a greater number of mitochondria in beta cells in GK rats compared to those in Wistar rats. Mitochondria in sucrose-fed GK rats were 2.4-fold greater in mean volume than those in untreated state. Without sucrose feeding, there was no significant difference in mitochondrial membrane potentials (MmPs) of isolated islets between Wistar and GK rats. MmPs were reduced by 44% in sucrose-fed GK rats but not influenced in sucrose-fed Wistar rats. Current results suggest that nutritional insults like sucrose feeding may exert deleterious effects on mitochondria, resulting in augmented beta cell loss in type 2 diabetes.
胰岛β细胞数量的逐渐减少是2型糖尿病的一个标志,在其病理过程中存在营养损伤。然而,其详细机制尚未完全明确。我们探讨了蔗糖饮食对自发性糖尿病模型Goto Kakizaki(GK)大鼠线粒体的影响。六周龄雄性GK大鼠经口给予30%蔗糖,持续2周。以喂食蔗糖的正常Wistar大鼠作为对照。与未处理的GK大鼠相比,喂食蔗糖的GK大鼠β细胞出现严重退化和死亡,线粒体破坏和肿胀,β细胞丢失更多。亚显微分析显示,与Wistar大鼠相比,GK大鼠β细胞中线粒体的平均体积更小,但数量更多。喂食蔗糖的GK大鼠线粒体平均体积比未处理状态下大2.4倍。不喂食蔗糖时,Wistar大鼠和GK大鼠分离胰岛的线粒体膜电位(MmPs)无显著差异。喂食蔗糖的GK大鼠MmPs降低了44%,但喂食蔗糖的Wistar大鼠不受影响。目前的结果表明,像蔗糖喂养这样的营养损伤可能会对线粒体产生有害影响,导致2型糖尿病中β细胞丢失增加。