在脂肪细胞中，脂联素分泌和GLUT4细胞膜转位对糖代谢都有重要作用。研究表明，Kinesin-1调节GLUT4细胞膜转位，但Kinesin-1在脂联素分泌中的作用未有报道。我们前期发现，脂联素与GLUT4充分共定位；Kinesin-1重链Kif5b与脂联素分泌泡、clathrin重链CHC和GGA1免疫共沉淀；Kif5b与CHC直接相互作用；沉默（或过表达）Kif5b显著抑制（或增强）脂联素分泌。据此提出假说：Kinesin-1通过clathrin识别GGA1包被的脂联素分泌泡，从而介导其分泌。这项研究，我们拟：1）通过3T3-L1细胞、脂肪细胞特异性敲除Kif5b小鼠和临床样本调查，进一步明确Kinesin-1在脂联素分泌中的作用；2）在3T3-L1细胞中沉默CHC和GGA1，探讨Kinesin-1识别脂联素分泌泡的分子机制。本研究将从胞内运输这个视角为揭示2型糖尿病的发病机制奠定基础。

Adiponectin secretion and GLUT4 translocation are important for glucose metabolism in adipocyte. It was found that Kinesin-1 mediated the translocation of GLUT4 to the plasma membrane. However, there is no report for the function of Kinesin-1 in adiponectin secretion. Our preliminary results revealed that adiponectin colocalized with GLUT4 in 3T3-L1 adipocytes; Kif5b (heavy chain of Kinesin-1) could be co-immunoprecipitated with adiponectin vesicles, clahtrin heavy chain (CHC) and GGA1; furthermore, knockdown (or overexpress) of Kif5b could significantly inhibit (or enhance) the secretion of adiponectin. Therefore, we hypothesize that Kinesin-1 is a very important motor protein that mediates the intracellular transportation and secretion of adiponectin; clathrin and GGA1 mediate the binding of Kinesin-1 and adiponectin vesicles. In this study, 1) shRNA mediated gene silencing in 3T3-L1 cells, mouse model with adipocyte specific knockout of Kinesin-1 and clinical samples will be used to analyze the function of Kinesin-1 in adiponectin secretion; 2) the molecular mechanisms that mediate the interaction of Kinesin-1 and adiponectin vescicles will be investigated. This study will provide new insights of the relationships between intracellular transportation and type 2 diabetes.