GP73 blockade alleviates abnormal glucose homeostasis in diabetic mice

内分泌学 内科学 糖尿病 葡萄糖稳态 平衡 碳水化合物代谢 链脲佐菌素 下调和上调 2型糖尿病 医学 葡萄糖转运蛋白 胰岛素 化学 胰岛素抵抗 生物化学 基因
作者
Xiaopan Yang,Xiaojing Fan,Jiangyue Feng,Tinghui Fan,Jingfei Li,Linfei Huang,Luming Wan,Huan Yang,Huilong Li,Jing Gong,Yanhong Zhang,Qi Gao,Fei Zheng,Lei Xu,Haotian Lin,Dandan Zhang,Hongbin Song,Yufei Wang,Xueping Ma,Zhiwei Sun
出处
期刊:Journal of Molecular Endocrinology [Bioscientifica]
卷期号:70 (2) 被引量:10
标识
DOI:10.1530/jme-22-0103
摘要

Golgi protein 73 (GP73), also called Golgi membrane protein 1 (GOLM1), is a resident Golgi type II transmembrane protein and is considered as a serum marker for the detection of a variety of cancers. A recent work revealed the role of the secreted GP73 in stimulating liver glucose production and systemic glucose homeostasis. Since exaggerated hepatic glucose production plays a key role in the pathogenesis of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM), GP73 may thus represent a potential therapeutic target for treating diabetic patients with pathologically elevated levels. Here, in this study, we found that the circulating GP73 levels were significantly elevated in T2DM and positively correlated with hemoglobin A1c. Notably, the aberrantly upregulated GP73 levels were indispensable for the enhanced protein kinase A signaling pathway associated with diabetes. In diet-induced obese mouse model, GP73 siRNA primarily targeting liver tissue was potently effective in alleviating abnormal glucose metabolism. Ablation of GP73 from whole animals also exerted a profound glucose-lowering effect. Importantly, neutralizing circulating GP73 improved glucose metabolism in streptozotocin (STZ) and high-fat diet/STZ-induced diabetic mice. We thus concluded that GP73 was a feasible therapeutic target for the treatment of diabetes.
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