Division of Endocrinology and Metabolism, Department of Internal Medicine, National Defense Medical Center, Tri-Service General Hospital, Taipei, Taiwan.
School of Dentistry, National Defense Medical Center, Taipei, Taiwan.
J Diabetes Investig. 2021 Apr;12(4):485-492. doi: 10.1111/jdi.13412. Epub 2020 Oct 13.
AIMS/INTRODUCTION: Obesity is characterized by disturbed adipocytokine expression and insulin resistance in adipocytes. Growth arrest-specific 6 (GAS6) is a gene encoding the Gas6 protein, which is expressed in fibroblasts, and its related signaling might be associated with adipose tissue inflammation, glucose intolerance and insulin resistance. The aim of this study was to investigate the associations among Gas6, adipocytokines and insulin resistance in adipocytes.
Mature Simpson Golabi Behmel Syndrome adipocytes were treated with high levels of insulin to mimic insulin resistance, and were examined for the expressions of Gas6, cytokines and adipocytokines from preadipocytes in differentiation. In an animal study, high-fat diet-induced obese mice were used to verify the Gas6 expression in vitro.
During the differentiation of adipocytes, the expression of Gas6 gradually decreased, and was obviously downregulated with adipocyte inflammation and insulin resistance. Gas6 levels were found to be in proportion to the expression of adiponectin, which has been regarded as closely relevant to improved insulin sensitivity after metformin treatment. Similar results were also confirmed in the animal study.
Our results suggest that Gas6 might modulate the expression of adiponectin, and might therefore be associated with insulin resistance in adipose tissues.
目的/引言：肥胖的特征是脂肪细胞中细胞因子表达紊乱和胰岛素抵抗。生长停滞特异性基因 6（GAS6）是编码 Gas6 蛋白的基因，该蛋白在成纤维细胞中表达，其相关信号可能与脂肪组织炎症、葡萄糖耐量异常和胰岛素抵抗有关。本研究旨在探讨 Gas6、脂肪细胞因子与脂肪细胞胰岛素抵抗之间的关系。
用高浓度胰岛素处理成熟的 Simpson-Golabi-Behmel 综合征脂肪细胞，以模拟胰岛素抵抗，并从分化前脂肪细胞中检测 Gas6、细胞因子和脂肪细胞因子的表达。在一项动物研究中，使用高脂肪饮食诱导肥胖的小鼠来验证体外 Gas6 的表达。
在脂肪细胞分化过程中，Gas6 的表达逐渐下降，并且随着脂肪细胞炎症和胰岛素抵抗而明显下调。Gas6 水平与脂联素的表达呈正相关，脂联素被认为与二甲双胍治疗后胰岛素敏感性的提高密切相关。动物研究也得到了类似的结果。
我们的结果表明，Gas6 可能调节脂联素的表达，因此可能与脂肪组织中的胰岛素抵抗有关。
