Centro de Microscopía Avanzada (CMA BIO-BIO), Universidad de Concepción, Concepción, Chile.
Institute of Biomedical Science, FH Joanneum Gesellschaft mbH University of Applied Sciences, Eggenberger Allee 13, 8020 Graz, Austria.
J Diabetes Res. 2018 May 29;2018:5697970. doi: 10.1155/2018/5697970. eCollection 2018.
The kidney is an insulin-sensitive organ involved in glucose homeostasis. One major effect of insulin is to induce glycogen storage in the liver and muscle. However, no significant glycogen stores are detected in normal kidneys, but diabetic subjects present a characteristic renal histopathological feature resulting from extensive glycogen deposition mostly in nonproximal tubules. The mechanism of renal glycogen accumulation is yet poorly understood. Here, we studied in situ glycogen accumulation in the kidney from diabetic IRS2-knockout mice and the effect of the insulin-mimetic agent sodium tungstate (NaW). IRS2-knockout mice displayed hyperglycemia and hyperinsulinemia. NaW only normalized glycemia. There was no evident morphological difference between kidneys from untreated wild-type (WT), NaW-treated WT, and untreated IRS2-knockout mice. However, NaW-treated IRS2-knockout mice showed tubular alterations resembling clear cells in the cortex, but not in the outer medulla, that were correlated with glycogen accumulation. Immunohistochemical detection of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase, mostly expressed by renal proximal tubules, showed that altered tubules were of proximal origin. Our preliminary study suggests that IRS2 differentially regulates glycogen accumulation in renal tubules and that NaW treatment in the context of IRS2 ablation induces abnormal glycogen accumulation in cortical proximal tubules.
肾脏是一个对胰岛素敏感的器官，参与葡萄糖稳态的调节。胰岛素的一个主要作用是诱导肝脏和肌肉中的糖原储存。然而，在正常肾脏中未检测到明显的糖原储存，但糖尿病患者表现出一种特征性的肾脏组织病理学特征，这是由于广泛的糖原沉积主要发生在近端小管。肾脏糖原积累的机制尚不清楚。在这里，我们研究了糖尿病 IRS2 敲除小鼠肾脏中的原位糖原积累以及胰岛素模拟剂钨酸钠 (NaW) 的作用。IRS2 敲除小鼠表现出高血糖和高胰岛素血症。NaW 仅使血糖正常化。未经处理的野生型 (WT)、NaW 处理的 WT 和未经处理的 IRS2 敲除小鼠的肾脏之间没有明显的形态差异。然而，NaW 处理的 IRS2 敲除小鼠的皮质中出现了类似于透明细胞的管状改变，但在外髓质中没有，这些改变与糖原积累有关。磷酸烯醇丙酮酸羧激酶 (PEPCK) 是一种糖异生酶，主要表达于肾脏近端小管，其免疫组织化学检测显示，改变的小管来源于近端。我们的初步研究表明，IRS2 差异调节肾脏小管中的糖原积累，并且在 IRS2 缺失的情况下，NaW 处理会诱导皮质近端小管中异常的糖原积累。
