Selective Insulin Resistance in the Kidney.
Selective Insulin Resistance in the Kidney.
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DOI：
10.1155/2016/5825170
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发表时间：
2016
影响因子：
--
通讯作者：
Seki G
中科院分区：
文献类型：
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作者：
Horita S;Nakamura M;Suzuki M;Satoh N;Suzuki A;Seki G
胰岛素抵抗的特征在于靶器官和组织（如肌肉和脂肪组织以及肝脏）的胰岛素敏感性减弱。胰岛素信号级联反应分为主要途径，如PI 3 K/Akt途径和MAPK/MEK途径。然而，在胰岛素抵抗中，这些途径并不同等受损。例如，在肝脏中，胰岛素受体底物（IRS）2途径对脂肪生成的抑制作用受损，而IRS 1途径的脂肪生成得以保留，从而引起高血糖症和高脂血症。最近有研究表明，胰岛素信号传导的选择性损伤也会导致胰岛素抵抗。在肾近端小管中，通过IRS 1的胰岛素信号传导被抑制，而通过IRS 2的胰岛素信号传导被保留。通过IRS 2的胰岛素信号传导继续刺激近端小管中的钠重吸收，并引起钠潴留、水肿和高血压。近端小管中IRS 1信号传导缺陷可能损害IRS 1介导的对血管生成的抑制，这可能通过保留葡萄糖产生而诱导高血糖。在肾小球中，IRS 1信号传导的损伤使足细胞和内皮细胞的结构和功能恶化，可能导致糖尿病肾病。本文主要介绍选择性胰岛素抵抗在肾脏，重点是近端小管。
Insulin resistance has been characterized as attenuation of insulin sensitivity at target organs and tissues, such as muscle and fat tissues and the liver. The insulin signaling cascade is divided into major pathways such as the PI3K/Akt pathway and the MAPK/MEK pathway. In insulin resistance, however, these pathways are not equally impaired. For example, in the liver, inhibition of gluconeogenesis by the insulin receptor substrate (IRS) 2 pathway is impaired, while lipogenesis by the IRS1 pathway is preserved, thus causing hyperglycemia and hyperlipidemia. It has been recently suggested that selective impairment of insulin signaling cascades in insulin resistance also occurs in the kidney. In the renal proximal tubule, insulin signaling via IRS1 is inhibited, while insulin signaling via IRS2 is preserved. Insulin signaling via IRS2 continues to stimulate sodium reabsorption in the proximal tubule and causes sodium retention, edema, and hypertension. IRS1 signaling deficiency in the proximal tubule may impair IRS1-mediated inhibition of gluconeogenesis, which could induce hyperglycemia by preserving glucose production. In the glomerulus, the impairment of IRS1 signaling deteriorates the structure and function of podocyte and endothelial cells, possibly causing diabetic nephropathy. This paper mainly describes selective insulin resistance in the kidney, focusing on the proximal tubule.