Inada Akari, Kanamori Hiroshi, Arai Hidenori, Akashi Tomoyuki, Araki Makoto, Weir Gordon C, Fukatsu Atsushi
SSP Stem Cell Unit, Kyushu University Graduate School of Medicine, Fukuoka, Japan.
J Cell Physiol. 2008 May;215(2):383-91. doi: 10.1002/jcp.21316.
We have previously found progressive diabetic nephropathy in inducible cAMP early repressor (ICER Igamma) transgenic (Tg) mice. The ICER Igamma Tg mouse is an interesting model of sustained hyperglycemia due to its low production of insulin and insulin-producing beta cells. Here in a longitudinal study we further analyzed diabetic nephropathy and structural and functional alterations in other organs, comparing our model with streptozotocin (STZ)-diabetic model mice. The high-dose STZ-diabetic model showed marked variation in blood glucose levels and severe toxicity of STZ in the liver and kidney. The low-dose STZ-diabetic model showed less toxicity, but the survival rate was very low. STZ-diabetic mice had much more variation of glomerular hypertrophy and sclerosis. Furthermore, non-specific toxicity of STZ or insulin injections to maintain optimal blood glucose levels might have another effect upon the diabetic renal changes. In contrast, ICER Igamma Tg mice exhibited a stable and progressive phenotype of diabetic kidney disease solely due to chronic hyperglycemia without other modulating factors. Thus, ICER Igamma Tg mouse has advantages for examining diabetic renal disease, and offers unique and very different perspectives compared to STZ model.
我们之前在诱导型环磷酸腺苷早期阻遏物（ICER Igamma）转基因（Tg）小鼠中发现了进行性糖尿病肾病。ICER Igamma Tg小鼠由于其胰岛素及胰岛素分泌β细胞产量低，是持续高血糖的一个有趣模型。在这项纵向研究中，我们进一步分析了糖尿病肾病以及其他器官的结构和功能改变，并将我们的模型与链脲佐菌素（STZ）诱导的糖尿病模型小鼠进行了比较。高剂量STZ糖尿病模型的血糖水平有显著变化，且STZ对肝脏和肾脏有严重毒性。低剂量STZ糖尿病模型的毒性较小，但存活率很低。STZ糖尿病小鼠的肾小球肥大和硬化变化更多。此外，为维持最佳血糖水平而注射STZ或胰岛素的非特异性毒性可能对糖尿病肾脏变化有其他影响。相比之下，ICER Igamma Tg小鼠仅由于慢性高血糖而呈现出稳定且进行性的糖尿病肾病表型，无其他调节因素。因此，ICER Igamma Tg小鼠在研究糖尿病肾病方面具有优势，与STZ模型相比提供了独特且非常不同的视角。
