Li Feng, Peng Ying, Zhang Manna, Yang Peng, Qu Shen
Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, Tong-Ji University, 301 Middle Yan-Chang Road, Shanghai, 200072, China.
Department of Endocrinology and Metabolism, Shanghai Clinical Center for Endocrine and Metabolic Diseases and Shanghai Institute of Endocrinology and Metabolism, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, 197 Rui-Jin 2nd Road, Shanghai, 200025, China.
Mol Cell Endocrinol. 2016 Nov 15;436:33-40. doi: 10.1016/j.mce.2016.07.019. Epub 2016 Jul 18.
Db/db mouse was used to study the underlying mechanisms by which Sleeve gastrectomy (SG) improves β-cell function. We investigated β-cell function, plasma active GLP-1 levels, the GLP-1R pathway in β cells and L cell differentiation. After SG, β-cell function was significantly increased, and the GLP-1R-PKCζ-PDX-1 pathway was active in β cells. Plasma active GLP-1 levels, as well as the number of L cells in the jejunum, were significantly increased after SG. The expression of early transcription factors (TF), including Ngn3, FoxA1 and Nkx2.2, was not compromised by chronic hyperglycemia. In contrast, the expression of the downstream TF PAX6 was affected, and this down-regulation could be reversed by SG. So, SG can maintain L cell differentiation, increase plasma active GLP-1 level, sustain the activation of the GLP-1R pathway and improve β cell function in Db/db mice. Our results show that SG can overall improve the function of the entero-insular axis.
使用db/db小鼠研究袖状胃切除术（SG）改善β细胞功能的潜在机制。我们研究了β细胞功能、血浆活性胰高血糖素样肽-1（GLP-1）水平、β细胞中的GLP-1受体（GLP-1R）途径以及L细胞分化。SG术后，β细胞功能显著增强，且GLP-1R-PKCζ-PDX-1途径在β细胞中被激活。SG术后，血浆活性GLP-1水平以及空肠中L细胞的数量显著增加。包括神经源性分化因子3（Ngn3）、叉头框蛋白A1（FoxA1）和NK2转录因子相关蛋白2（Nkx2.2）在内的早期转录因子（TF）的表达不受慢性高血糖的影响。相反，下游TF配对盒蛋白6（PAX6）的表达受到影响，而这种下调可通过SG逆转。因此，SG可维持L细胞分化，提高血浆活性GLP-1水平，维持GLP-1R途径的激活并改善db/db小鼠的β细胞功能。我们的结果表明，SG可整体改善肠-胰岛轴的功能。
