Combs T P, Berg A H, Obici S, Scherer P E, Rossetti L
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
J Clin Invest. 2001 Dec;108(12):1875-81. doi: 10.1172/JCI14120.
Intraperitoneal injection of purified recombinant Acrp30 lowers glucose levels in mice. To gain insight into the mechanism(s) of this hypoglycemic effect, purified recombinant Acrp30 was infused in conscious mice during a pancreatic euglycemic clamp. In the presence of physiological hyperinsulinemia, this treatment increased circulating Acrp30 levels by approximately twofold and stimulated glucose metabolism. The effect of Acrp30 on in vivo insulin action was completely accounted for by a 65% reduction in the rate of glucose production. Similarly, glucose flux through glucose-6-phosphatase (G6Pase) decreased with Acrp30, whereas the activity of the direct pathway of glucose-6-phosphate biosynthesis, an index of hepatic glucose phosphorylation, increased significantly. Acrp30 did not affect the rates of glucose uptake, glycolysis, or glycogen synthesis. These results indicate that an acute increase in circulating Acrp30 levels lowers hepatic glucose production without affecting peripheral glucose uptake. Hepatic expression of the gluconeogenic enzymes phosphoenolpyruvate carboxykinase and G6Pase mRNAs was reduced by more than 50% following Acrp30 infusion compared with vehicle infusion. Thus, a moderate rise in circulating levels of the adipose-derived protein Acrp30 inhibits both the expression of hepatic gluconeogenic enzymes and the rate of endogenous glucose production.
腹腔注射纯化的重组Acrp30可降低小鼠的血糖水平。为深入了解这种降血糖作用的机制，在胰腺正常血糖钳夹期间，将纯化的重组Acrp30注入清醒小鼠体内。在生理性高胰岛素血症存在的情况下，这种处理使循环中的Acrp30水平增加了约两倍，并刺激了葡萄糖代谢。Acrp30对体内胰岛素作用的影响完全是由于葡萄糖生成速率降低了65%。同样，Acrp30使通过葡萄糖-6-磷酸酶（G6Pase）的葡萄糖通量降低，而作为肝葡萄糖磷酸化指标的葡萄糖-6-磷酸生物合成直接途径的活性则显著增加。Acrp30不影响葡萄糖摄取、糖酵解或糖原合成的速率。这些结果表明，循环中Acrp30水平的急性升高可降低肝葡萄糖生成，而不影响外周葡萄糖摄取。与注射赋形剂相比，注射Acrp30后，糖异生酶磷酸烯醇丙酮酸羧激酶和G6Pase mRNA的肝表达降低了50%以上。因此，脂肪源性蛋白Acrp30循环水平的适度升高可抑制肝糖异生酶的表达和内源性葡萄糖生成速率。
