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标题：LRRK2 Inhibition Ameliorates Dexamethasone-Induced Glucose Intolerance via Prevents Impairment in GLUT4 Membrane Translocation in Adipocytes
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作者：Motoki Imai ; Fumitaka Kawakami ; Makoto Kubo 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2020
卷号：43
期号：11
页码：1660-1668
DOI：10.1248/bpb.b20-00377
出版社：The Pharmaceutical Society of Japan
摘要：Mutations in the leucine-rich repeat kinase 2 ( LRRK2 ) gene are associated with Parkinson’s disease. LRRK2 is a large protein with multiple functional domains, including a guanosine 5′-triphosphate (GTP)-binding domain and a protein kinase domain. Recent studies indicated that the members of the Rab GTPase family, Rab8a and Rab10, which are involved in the membrane transport of the glucose transporter type 4 (GLUT4) during insulin-dependent glucose uptake, are phosphorylated by LRRK2. However, the physiological role of LRRK2 in the regulation of glucose metabolism is largely unknown. In the present study, we investigated the role of LRRK2 using dexamethasone (DEX)-induced glucose intolerance in mice. LRRK2 knockout (KO) mice exhibited suppressed glucose intolerance, even after treatment with DEX. The phosphorylation of LRRK2, Rab8a and Rab10 was increased in the adipose tissues of DEX-treated wild-type mice. In addition, inhibition of the LRRK2 kinase activity prevented the DEX-induced inhibition of GLUT4 membrane translocation and glucose uptake in cultured 3T3-L1 adipocytes. These results suggest that LRRK2 plays an important role in glucose metabolism in adipose tissues.
关键词：leucine-rich repeat kinase 2 (LRRK2);glucose transporter 4 (GLUT4);adipocyte;glucose intolerance;dexamethasone