Yamanaka M, Tsuchida A, Nakagawa T, Nonomura T, Ono-Kishino M, Sugaru E, Noguchi H, Taiji M
Dainippon Sumitomo Pharma Co. Ltd, Drug Research Division, Pharmacology Research Laboratories, Discovery Pharmacology Group I, Kasugadenaka, Konohana-ku, Osaka, Japan.
Diabetes Obes Metab. 2007 Jan;9(1):59-64. doi: 10.1111/j.1463-1326.2006.00572.x.
Repetitive subcutaneous or intracerebroventricular administration of brain-derived neurotrophic factor (BDNF) ameliorates glucose metabolism and enhances energy expenditure in obese diabetic C57BL/KsJ-db/db mice. To explore the mechanism of action through which BDNF regulates glucose metabolism, we examined the effects of BDNF on glucose utilization and norepinephrine (NE) content in peripheral tissues of diabetic mice.
[(14)C]2-deoxyglucose ([(14)C]2-DG) uptake into peripheral tissues was analysed after intravenous injection of [(14)C]2-DG in db/db and normal C57BL/6 mice, and [(14)C]2-DG uptake and NE content in peripheral tissues were analysed after subcutaneous administration of BDNF (20 mg/kg) to male db/db and normal mice for 8 days.
[(14)C]2-DG uptake in the diaphragm, heart, gastrocnemius, soleus and interscapular brown adipose tissue (BAT) of db/db mice was significantly lower than in normal mice. Repetitive administration of BDNF to db/db mice for 8 days enhanced [(14)C]2-DG uptake in the diaphragm, heart, soleus, BAT and liver. The NE content in heart, skeletal muscle, interscapular BAT and liver of db/db mice given BDNF was high compared with db/db mice given vehicle, whereas no significant change in NE content in peripheral tissues was observed in normal mice given BDNF and those given vehicle. BDNF did not affect [(14)C]2-DG uptake or NE content in the white adipose tissue of db/db mice.
These data indicate that BDNF ameliorates glucose metabolism by enhancement of glucose utilization in muscle and BAT, with this effect caused by modulation of the central and peripheral nervous systems.
重复皮下或脑室内注射脑源性神经营养因子（BDNF）可改善肥胖糖尿病C57BL/KsJ-db/db小鼠的葡萄糖代谢并增加能量消耗。为探究BDNF调节葡萄糖代谢的作用机制，我们检测了BDNF对糖尿病小鼠外周组织葡萄糖利用和去甲肾上腺素（NE）含量的影响。
给db/db小鼠和正常C57BL/6小鼠静脉注射[(14)C]2-脱氧葡萄糖（[(14)C]2-DG）后，分析外周组织对[(14)C]2-DG的摄取情况；给雄性db/db小鼠和正常小鼠皮下注射BDNF（20 mg/kg），持续8天，之后分析外周组织对[(14)C]2-DG的摄取及NE含量。
db/db小鼠膈肌、心脏、腓肠肌、比目鱼肌和肩胛间棕色脂肪组织（BAT）对[(14)C]2-DG的摄取显著低于正常小鼠。给db/db小鼠重复注射BDNF 8天可增强膈肌、心脏、比目鱼肌、BAT和肝脏对[(14)C]2-DG的摄取。与注射赋形剂的db/db小鼠相比，注射BDNF的db/db小鼠心脏、骨骼肌、肩胛间BAT和肝脏中的NE含量较高，而给正常小鼠注射BDNF和赋形剂后，外周组织中NE含量未观察到显著变化。BDNF对db/db小鼠白色脂肪组织中[(14)C]2-DG摄取或NE含量无影响。
这些数据表明，BDNF通过增强肌肉和BAT中的葡萄糖利用来改善葡萄糖代谢，这种作用是由中枢和外周神经系统的调节引起的。
