Robinson A M, Williamson D H
Biochem J. 1977 Dec 15;168(3):465-74. doi: 10.1042/bj1680465.
Inhibition of glucose uptake by acetoacetate and relief of this inhibition by insulin found previously in slices of rat mammary gland [Williamson, McKeown & Ilic (1975) Biochem. J. 150. 145-152] was confirmed in acini, which represent a more homogeneous population of cells. Glycerol (1mM) behaved like insulin (50 minuits/ml) in its ability to relieve the inhibition of glucose (5 mM) utilization caused by acetoacetate (2 mM) in acini. Both glycerol and insulin reversed the increase in [citrate] and the decrease in [glycerol 3-phosphate] and the [lactate]/[pyruvate] ratio in the presence of acetoacetate. Lipogenesis from 3H2O, [3-14C] acetoacetate, [1-14C]- and [6-14C]-glucose was stimulated, whereas 14CO2 formation from [3-14C]acetoacetate was decreased. Neither insulin nor glycerol relieved the acetoacetate inhibition of glucose uptake when lipogenesis was inhibited by 5-(tetradecyloxy)-2-furoic acid. From measurements of [3-14C]acetoacetate incorporation into lipid in the various situations it is suggested that a cytosolic pathway for acetoacetate utilization may exist in rat mammary gland. In the absence of acetoacetate, glycerol inhibited glucose utilization by 60% and increased both [glycerol 3-phosphate] and the [lactate/[pyruvate] ratio. Possible ways in which glycerol may mimic the effects of insulin are discussed.
先前在大鼠乳腺切片中发现的乙酰乙酸对葡萄糖摄取的抑制作用以及胰岛素对这种抑制作用的解除作用[威廉姆森、麦基翁和伊利克(1975年),《生物化学杂志》150卷,145 - 152页]在腺泡中得到了证实,腺泡代表了更均匀的细胞群体。甘油(1毫摩尔)在解除腺泡中乙酰乙酸(2毫摩尔)对葡萄糖(5毫摩尔)利用的抑制作用方面,表现得与胰岛素(50分钟/毫升)相似。在存在乙酰乙酸的情况下,甘油和胰岛素都能逆转柠檬酸浓度的升高、磷酸甘油浓度的降低以及乳酸/丙酮酸比值的降低。由3H2O、[3 - 14C]乙酰乙酸、[1 - 14C] - 和[6 - 14C] - 葡萄糖生成脂肪的过程受到刺激,而由[3 - 14C]乙酰乙酸生成14CO2的过程则减少。当脂肪生成被5 - (十四烷氧基) - 2 - 呋喃甲酸抑制时,胰岛素和甘油都不能解除乙酰乙酸对葡萄糖摄取的抑制作用。从在各种情况下对[3 - 14C]乙酰乙酸掺入脂质的测量结果来看,提示大鼠乳腺中可能存在一条乙酰乙酸利用的胞质途径。在没有乙酰乙酸的情况下,甘油使葡萄糖利用降低了60%,并使磷酸甘油浓度以及乳酸/丙酮酸比值都升高。文中讨论了甘油可能模拟胰岛素作用的几种可能方式。