Infusion of mesenchymal stem cells ameliorates hyperglycemia in type 2 diabetic rats: identification of a novel role in improving insulin sensitivity.

Infusion of mesenchymal stem cells ameliorates hyperglycemia in type 2 diabetic rats: identification of a novel role in improving insulin sensitivity.
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间充质干细胞输注可改善 2 型糖尿病大鼠的高血糖:确定改善胰岛素敏感性的新作用。

DOI:
10.2337/db11-1141
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发表时间:
2012-06
期刊:
影响因子:
7.7
通讯作者:
Han W
Han W
中科院分区:
医学1区
文献类型:
--
作者:
Si Y;Zhao Y;Hao H;Liu J;Guo Y;Mu Y;Shen J;Cheng Y;Fu X;Han W

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间充质干细胞(MSC)的输注已被证明可以有效地降低糖尿病患者的血糖,但所涉及的机制无法通过其促进胰岛再生的潜在作用得到充分解释。因此,我们假设,输注的MSC也可能有助于改善外周胰岛素靶组织的胰岛素抵抗。为了验证这一假设,我们通过高脂饮食/链脲佐菌素(STZ)诱导糖尿病大鼠模型,在STZ注射后的早期(7天)或晚期(21天)进行MSC输注,然后评估MSC输注的治疗效果并探讨可能的机制。MSC输注可改善2型糖尿病(T2 D)大鼠的高血糖。在早期阶段输注MSC不仅促进β细胞功能,而且改善胰岛素抵抗,而在晚期阶段输注仅改善胰岛素抵抗。输注MSC导致胰岛素靶组织中GLUT 4表达增加以及磷酸化胰岛素受体底物1(IRS-1)和Akt(蛋白激酶B)升高。这是MSC治疗改善T2 D胰岛素敏感性的第一份报告。这些数据表明,多种作用和机制参与了MSC改善T2 D高血糖症的功效。
Infusion of mesenchymal stem cells (MSCs) has been shown to effectively lower blood glucose in diabetic individuals, but the mechanism involved could not be adequately explained by their potential role in promoting islet regeneration. We therefore hypothesized that infused MSCs might also contribute to amelioration of the insulin resistance of peripheral insulin target tissues. To test the hypothesis, we induced a diabetic rat model by high-fat diet/streptozotocin (STZ) administration, performed MSC infusion during the early phase (7 days) or late phase (21 days) after STZ injection, and then evaluated the therapeutic effects of MSC infusion and explored the possible mechanisms involved. MSC infusion ameliorated hyperglycemia in rats with type 2 diabetes (T2D). Infusion of MSCs during the early phase not only promoted β-cell function but also ameliorated insulin resistance, whereas infusion in the late phase merely ameliorated insulin resistance. Infusion of MSCs resulted in an increase of GLUT4 expression and an elevation of phosphorylated insulin receptor substrate 1 (IRS-1) and Akt (protein kinase B) in insulin target tissues. This is the first report of MSC treatment improving insulin sensitivity in T2D. These data indicate that multiple roles and mechanisms are involved in the efficacy of MSCs in ameliorating hyperglycemia in T2D.
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