Liu Hong, Zhan Yan-Li, Luo Guo-Jing, Zou Ling-Ling, Li Yun, Lu Hong-Yun
Department of Nutrition, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
Department of Endocrinology & Metabolism, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong, People's Republic of China.
Diabetes Metab Syndr Obes. 2020 Sep 1;13:3075-3087. doi: 10.2147/DMSO.S253097. eCollection 2020.
Glucagon-like peptide-1 (GLP-1) has been reported to have beneficial impacts on improving human's metabolism and ameliorating insulin resistance. While insulin is another important and conventional drug in diabetes treatment, but it has an adverse effect on weight gain.
To make sure whether GLP-1 and insulin play different roles in human adipose-derived stem cells (hADSCs).
We examined the in vitro roles and molecular mechanisms of liraglutide, a GLP-1 analogue, and human insulin on hADSCs isolated from subcutaneous adipose tissue. Different concentrations (0, 0.1, 1, 10, 100nM) of liraglutide and insulin were added to proliferation and differentiation medium of hADSCs, respectively.
Liraglutide inhibits while insulin promotes the proliferation and differentiation at the concentration of 100nM. Moreover, the levels of GSK-3 increase during differentiation and liraglutide could down-regulate it when compared with insulin. We also find that the activation of phosphorylated GSK-3α and GSK-3β is involved in the differentiation roles. And classical and non-classical Wnt pathways all play roles in the differentiation, which are characterized with the up/down-regulation of the expression of adipogenesis genes such as PPAR-γ and CEBP-α.
Liraglutide and insulin have contrary effects on the proliferation and adipogenesis via Wnt pathway in primary cultured ADSCs. Those effects could partly explain the different roles of GLP-1 and insulin on weight gain and insulin resistance.
据报道，胰高血糖素样肽-1（GLP-1）对改善人体代谢和减轻胰岛素抵抗具有有益作用。胰岛素是糖尿病治疗中另一种重要的传统药物，但它有导致体重增加的副作用。
确定GLP-1和胰岛素在人脂肪来源干细胞（hADSCs）中是否发挥不同作用。
我们研究了GLP-1类似物利拉鲁肽和人胰岛素对从皮下脂肪组织分离的hADSCs的体外作用及分子机制。分别将不同浓度（0、0.1、1、10、100nM）的利拉鲁肽和胰岛素添加到hADSCs的增殖和分化培养基中。
在100nM浓度下，利拉鲁肽抑制而胰岛素促进hADSCs的增殖和分化。此外，在分化过程中GSK-3水平升高，与胰岛素相比，利拉鲁肽可下调其水平。我们还发现磷酸化的GSK-3α和GSK-3β的激活参与了分化作用。经典和非经典Wnt通路在分化过程中均发挥作用，其特征是脂肪生成基因如PPAR-γ和CEBP-α表达的上调/下调。
利拉鲁肽和胰岛素在原代培养的ADSCs中通过Wnt通路对增殖和脂肪生成具有相反作用。这些作用可以部分解释GLP-1和胰岛素在体重增加和胰岛素抵抗方面的不同作用。
