Pancreatic stellate cells in the islets as a novel target to preserve the pancreatic β-cell mass and function.,Journal of Diabetes Investigation

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Pancreatic stellate cells in the islets as a novel target to preserve the pancreatic β-cell mass and function.
Journal of Diabetes Investigation ( IF 3.1 ) Pub Date : 2020-01-24 , DOI: 10.1111/jdi.13202
Yeoree Yang ₁ , Ji-Won Kim ₁ , Heon-Seok Park ₁ , Eun-Young Lee ₁ , Kun-Ho Yoon ₁

Affiliation

There are numerous lines of clinical evidence that inhibition of the renin–angiotensin system (RAS) can prevent and delay the development of diabetes. Also, the role of RAS in the pathogenesis of diabetes, including insulin resistance and β‐cell dysfunction, has been extensively investigated. Nevertheless, this role had not yet been fully shown. A variety of possible protective mechanisms for RAS blockers in the regulation of glucose homeostasis have been suggested. However, the direct effect on pancreatic islet fibrosis has only recently been spotlighted. Various degrees of islet fibrosis are often observed in the islets of patients with type 2 diabetes mellitus, which can be associated with a decrease in β‐cell mass and function in these patients. Pancreatic stellate cells are thought to be deeply involved in this islet fibrosis. In this process, the activation of RAS in islets is shown to transform quiescent pancreatic stellate cells into the activated form, stimulates their proliferation and consequently leads to islet fibrotic destruction. In this article, we introduce existing clinical and experimental evidence for diabetes prevention through inhibition of RAS, and review the responsible local RAS signaling pathways in pancreatic stellate cells. Finally, we propose possible targets for the prevention of islet fibrosis.

中文翻译：

胰岛中的胰腺星状细胞作为保护胰腺 β 细胞质量和功能的新靶点。

大量临床证据表明，抑制肾素-血管紧张素系统（RAS）可以预防和延缓糖尿病的发展。此外，RAS 在糖尿病发病机制中的作用，包括胰岛素抵抗和 β 细胞功能障碍，已得到广泛研究。然而，这一作用尚未完全发挥出来。已经提出了 RAS 阻滞剂在调节葡萄糖稳态中的多种可能的保护机制。然而，对胰岛纤维化的直接影响最近才受到关注。在 2 型糖尿病患者的胰岛中经常观察到不同程度的胰岛纤维化，这可能与这些患者的 β 细胞质量和功能下降有关。胰腺星状细胞被认为与这种胰岛纤维化密切相关。在此过程中，胰岛中 RAS 的激活可将静止的胰腺星状细胞转化为激活的形式，刺激其增殖，从而导致胰岛纤维化破坏。在本文中，我们介绍了通过抑制 RAS 预防糖尿病的现有临床和实验证据，并回顾了胰腺星状细胞中负责的局部 RAS 信号通路。最后，我们提出了预防胰岛纤维化的可能目标。

更新日期：2020-01-24

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