RhoB Loss Prevents Streptozotocin-Induced Diabetes and Ameliorates Diabetic Complications in Mice
RhoB Loss Prevents Streptozotocin-Induced Diabetes and Ameliorates Diabetic Complications in Mice
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DOI：
10.1016/j.ajpath.2010.11.040
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发表时间：
2011-01-01
影响因子：
6
通讯作者：
Benjamin, Laura E.
中科院分区：
文献类型：
--
作者：
Bravo-Nuevo, Arturo;Sugimoto, Hikaru;Benjamin, Laura E.
RhoB 是一种早期反应基因，其表达会因多种细胞应激而升高；该基因在癌症、巨噬细胞运动和细胞凋亡中发挥重要作用。这些因素对于 1 型糖尿病和相关并发症的发生至关重要。本研究探讨了 RhoB 在 β 细胞耗竭和高血糖相关并发症中的作用，并测试他汀类药物对血糖控制的多效性是否依赖于 RhoB。我们用链脲佐菌素 (STZ) 诱导 RhoB(+/+)、RhoB(+/-) 和 RboB(-/-) 小鼠的 β 细胞耗竭。通过葡萄糖耐量和胰岛损失来评估糖尿病状态。 RhoB(-/-) 小鼠表现出 STZ 诱导的糖尿病严重程度显着降低；仅 13% 的 STZ 处理的 RhoB 缺失动物出现高血糖，而野生型对照动物中这一比例为 61%。还评估了与糖尿病相关的并发症，例如伤口愈合率和肾病的发病率。与 RhoB(+/+) 动物相比，高血糖 RhoB(-/-) 小鼠肾病迹象较少，伤口愈合更快。在评估同时接受 STZ 和辛伐他汀治疗的小鼠的糖尿病状况后，我们得出结论，他汀类药物改善血糖控制的作用与 RhoB 无关。我们认为 RhoB 是糖尿病的调节剂，对于诱导 β 细胞损失很重要。抑制 RhoB 表达可能在治疗糖尿病和相关并发症中具有潜在的应用。 （Am J Pathol 2011，178：245-252。DOI：10.1016/j.ajpath.2010.11.040）
RhoB is an early-response gene whose expression is elevated by multiple cellular stresses; this gene plays an important role in cancer, macrophage motility, and apoptosis. These factors are essential for the onset of type 1 diabetes mellitus and related complications. This study explores the role of RhoB in beta-cell depletion and hyperglycemia-associated complications and tests whether the pleiotropic effect of statins on glycemic control is RhoB dependent. We induced beta-cell depletion in RhoB(+/+), RhoB(+/-), and RboB(-/-) mice with streptozotocin (STZ). Diabetic status was assessed by glucose tolerance and pancreatic islet loss. RhoB(-/-) mice showed a significant reduction in the severity of STZ-induced diabetes; only 13% of the STZ-treated RhoB-null animals became hyperglycemic, as opposed to 61% of the wild-type controls. Diabetes-related complications, such as wound healing rate and onset of nephropathy, were also assessed. Hyperglycemic RhoB(-/-) mice had fewer signs of nephropathy and showed faster wound healing than RhoB(+/+) animals. After assessing the diabetic status of mice treated simultaneously with STZ and simvastatin, we conclude that the effect of statins in improving glycemic control is RhoB independent. We propose that RhoB is a modifier of diabetes, important for the induction of beta-cell loss. Suppression of RhoB expression may have potential application in the treatment of diabetes and associated complications. (Am J Pathol 2011, 178:245-252. DOI: 10.1016/j.ajpath.2010.11.040)