Department of Nutrition, Food Science and Physiology, University of Navarra, Pamplona, Spain.
Nutrition Research Centre, University of Navarra, Pamplona, Spain.
Acta Physiol (Oxf). 2019 Aug;226(4):e13283. doi: 10.1111/apha.13283. Epub 2019 May 11.
The facilitative glucose transporter GLUT12 was isolated from the breast cancer cell line MCF-7 by its homology with GLUT4. GLUT12 is expressed in insulin-sensitive tissues such as adipose tissue. The aim of this work was to investigate GLUT12 expression and hormonal regulation in 3T3-L1 adipocytes and in adipose tissue of lean and diet-induced obese mice.
Uptake studies were performed using radio-labelled sugars; α-methyl-d-glucose (αMG) was used as specific substrate of GLUT12. Expression and localization of GLUT12 in adipocytes were investigated by western blot and immunohistochemical methods.
GLUT12 is expressed in the peri-nuclear region of mouse adipocytes. Insulin, by AKT activation, and TNF-α, by AMPK activation, increase αMG uptake by inducing GLUT12 translocation to the membrane. In contrast, leptin and adiponectin decrease GLUT12 activity through its internalization. Under hypoxia conditions GLUT12 expression is upregulated. The response of GLUT12 to TNF-α, leptin, adiponectin and hypoxia is the opposite to that of GLUT4. In diet-induced obese mice and obese subjects, GLUT12 protein is decreased. Intraperitoneal injection of insulin increases AKT phosphorylation and GLUT12 expression, but this effect is lost in obese animals.
We hypothesize that GLUT12 would contribute to modulate sugar absorption in physiological and pathophysiological situations such as obesity.
通过与 GLUT4 的同源性，从乳腺癌细胞系 MCF-7 中分离出易化葡萄糖转运蛋白 GLUT12。GLUT12 在胰岛素敏感组织如脂肪组织中表达。本工作旨在研究 3T3-L1 脂肪细胞和瘦鼠及饮食诱导肥胖鼠脂肪组织中 GLUT12 的表达和激素调节。
使用放射性标记糖进行摄取研究；α-甲基-d-葡萄糖（αMG）用作 GLUT12 的特异性底物。通过 Western blot 和免疫组织化学方法研究 GLUT12 在脂肪细胞中的表达和定位。
GLUT12 在小鼠脂肪细胞的核周区表达。胰岛素通过 AKT 激活，TNF-α 通过 AMPK 激活，通过诱导 GLUT12 向膜易位来增加 αMG 摄取。相反，瘦素和脂联素通过内化降低 GLUT12 活性。在缺氧条件下，GLUT12 表达上调。GLUT12 对 TNF-α、瘦素、脂联素和缺氧的反应与 GLUT4 相反。在饮食诱导肥胖的小鼠和肥胖个体中，GLUT12 蛋白减少。胰岛素腹腔注射增加 AKT 磷酸化和 GLUT12 表达，但在肥胖动物中这种作用丧失。
我们假设 GLUT12 将有助于调节肥胖等生理和病理生理情况下的糖吸收。
