Mercer S W, Williamson D H
Biochem J. 1987 Feb 15;242(1):235-43. doi: 10.1042/bj2420235.
Depression of carbohydrate digestion by oral administration of acarbose, a glucosidase inhibitor, led to a 75% inhibition of the re-activation of lipogenesis in vivo in the mammary gland of 18 h-starved lactating rats refed with 5 g of chow diet. Rates of [1-14C]glucose incorporation in vitro into lipid and CO2 in mammary-gland acini isolated from refed animals were elevated compared with acini from starved rats, but acarbose treatment completely prevented this stimulation. Gastric intubation of glucose led to a large stimulation of lipogenesis in the mammary gland of starved lactating rats, similar to that induced by refeeding with chow diet; this was dependent on the amount of glucose given and the time elapsed between glucose administration and injection of 3H2O for the measurement of lipogenesis. The switch-on of lipogenesis in the mammary gland of starved lactating rats, by refeeding or by intubation of glucose, was associated with a decrease in the ratio of [glucose 6-phosphate]/[fructose 1,6-bisphosphate] in the gland, indicative of an increase in phosphofructokinase activity. A time-course study revealed that the ratio decreased rapidly over the first 30 min of chow refeeding, after which a large surge in lipogenesis was seen. Acarbose, given 25 min after the onset of refeeding, led to a stepwise increase in the ratio, in parallel with the observed decrease in lipogenic activity. It is concluded that the control of lipogenesis in the mammary gland is closely linked to the availability of dietary carbohydrate. An important site of regulation of lipogenesis in the gland appears to be at the level of phosphofructokinase. A possible role of insulin in the regulation of phosphofructokinase activity, and the acute modulation of insulin-sensitivity in the gland during the starved-refed transition, are discussed.
口服葡萄糖苷酶抑制剂阿卡波糖抑制碳水化合物消化，导致18小时饥饿后再喂5克普通饲料的泌乳大鼠乳腺中脂肪生成再激活受到75%的抑制。与饥饿大鼠的腺泡相比，从再喂动物分离的乳腺腺泡中，体外[1-14C]葡萄糖掺入脂质和二氧化碳的速率有所升高，但阿卡波糖处理完全阻止了这种刺激。胃内插管注入葡萄糖可极大地刺激饥饿泌乳大鼠乳腺中的脂肪生成，类似于普通饲料再喂所诱导的情况；这取决于给予的葡萄糖量以及给予葡萄糖与注射用于测量脂肪生成的3H2O之间经过的时间。通过再喂或胃内插管注入葡萄糖使饥饿泌乳大鼠乳腺中的脂肪生成开启，这与腺体中[6-磷酸葡萄糖]/[1,6-二磷酸果糖]的比值降低有关，表明磷酸果糖激酶活性增加。一项时间进程研究表明，再喂普通饲料的最初30分钟内该比值迅速下降，之后脂肪生成出现大幅激增。再喂开始25分钟后给予阿卡波糖，导致该比值逐步升高，与观察到的脂肪生成活性降低平行。得出的结论是，乳腺中脂肪生成的控制与膳食碳水化合物的可利用性密切相关。腺体中脂肪生成调节的一个重要位点似乎在磷酸果糖激酶水平。讨论了胰岛素在调节磷酸果糖激酶活性中的可能作用，以及在饥饿-再喂转变期间腺体中胰岛素敏感性的急性调节。
