Institut Cochin, Université de Paris, INSERM U1016, CNRS UMR 8104, 75014 Paris, France.
Cordeliers Research Centre, INSERM, Immunity and Metabolism in Diabetes Laboratory, Université de Paris, 75006 Paris, France.
Cells. 2022 Mar 8;11(6):924. doi: 10.3390/cells11060924.
In human type 2 diabetes, adipose tissue plays an important role in disturbing glucose homeostasis by secreting factors that affect the function of cells and tissues throughout the body, including insulin-producing pancreatic beta cells. We aimed here at studying the paracrine effect of stromal cells isolated from subcutaneous and omental adipose tissue on human beta cells. We developed an in vitro model wherein the functional human beta cell line EndoC-βH1 was treated with conditioned media from human adipose tissues. By using RNA-sequencing and western blotting, we determined that a conditioned medium derived from omental stromal cells stimulates several pathways, such as STAT, SMAD and RELA, in EndoC-βH1 cells. We also observed that upon treatment, the expression of beta cell markers decreased while dedifferentiation markers increased. Loss-of-function experiments that efficiently blocked specific signaling pathways did not reverse dedifferentiation, suggesting the implication of more than one pathway in this regulatory process. Taken together, we demonstrate that soluble factors derived from stromal cells isolated from human omental adipose tissue signal human beta cells and modulate their identity.
在人类 2 型糖尿病中，脂肪组织通过分泌影响全身细胞和组织功能的因子，在扰乱葡萄糖内稳态方面发挥重要作用，包括产生胰岛素的胰腺β细胞。我们旨在研究从皮下和网膜脂肪组织分离的基质细胞对人β细胞的旁分泌作用。我们开发了一种体外模型，其中功能性人β细胞系 EndoC-βH1 用来自人脂肪组织的条件培养基处理。通过使用 RNA 测序和 Western blot，我们确定源自网膜基质细胞的条件培养基可刺激 EndoC-βH1 细胞中的几个途径，如 STAT、SMAD 和 RELA。我们还观察到，在治疗后，β细胞标志物的表达减少，而去分化标志物的表达增加。有效阻断特定信号通路的功能丧失实验并没有逆转去分化，这表明在这个调节过程中涉及不止一个途径。总之，我们证明了源自人网膜脂肪组织分离的基质细胞衍生的可溶性因子可向人β细胞发出信号并调节其特性。
