Sowell M O, Boggs K P, Robinson K A, Dutton S L, Buse M G
Department of Medicine, Medical University of South Carolina, Charleston 29425.
Am J Physiol. 1991 Feb;260(2 Pt 1):E247-56. doi: 10.1152/ajpendo.1991.260.2.E247.
Phospholipase C (PLC), an enzyme that increases endogenous 1,2-diacylglycerol (DAG), caused dose-dependent stimulation of 2-deoxy-D-glucose (2-DG) uptake in rat soleus muscles; the maximal effect was less than that of insulin. In denervated muscles the effect of insulin on 2-DG uptake was markedly reduced, whereas the response to PLC was identical to that of control muscles. Both PLC and insulin stimulated glucose incorporation into glycogen in control but not in denervated solei. Amino acid transport was unaffected by PLC; however, the enzyme completely inhibited the stimulation of amino acid transport by insulin. PLC did not activate the insulin receptor tyrosine kinase but decreased activation of the receptor by insulin in vivo. Basal muscle DAG content increased after denervation. Incubation with PLC markedly increased DAG in control and in denervated muscle. Insulin increased total DAG mass less than PLC in control muscles and did not affect DAG in denervated muscles. In media without added Ca2+, PLC stimulation of DAG production was impaired, and 2-DG uptake was unresponsive to PLC. The data are consistent with, but do not prove, that a subpopulation of DAGs may participate in insulin-mediated stimulation of glucose transport. They also suggest that the denervation-induced insulin resistance of glucose transport may reflect impaired generation of certain DAGs involved in the signaling cascade.
磷脂酶C（PLC）是一种可增加内源性1,2 - 二酰甘油（DAG）的酶，它能引起大鼠比目鱼肌对2 - 脱氧 - D - 葡萄糖（2 - DG）摄取的剂量依赖性刺激；最大效应小于胰岛素。在去神经支配的肌肉中，胰岛素对2 - DG摄取的作用明显降低，而对PLC的反应与对照肌肉相同。在对照比目鱼肌中，PLC和胰岛素均可刺激葡萄糖掺入糖原，但在去神经支配的比目鱼肌中则不然。氨基酸转运不受PLC影响；然而，该酶完全抑制了胰岛素对氨基酸转运的刺激作用。PLC未激活胰岛素受体酪氨酸激酶，但在体内降低了胰岛素对该受体的激活作用。去神经支配后，肌肉基础DAG含量增加。与PLC孵育可显著增加对照肌肉和去神经支配肌肉中的DAG。在对照肌肉中，胰岛素增加的总DAG量少于PLC，且对去神经支配肌肉中的DAG无影响。在不添加Ca2 +的培养基中，PLC对DAG产生的刺激作用受损，且2 - DG摄取对PLC无反应。这些数据与但不能证明一部分DAG可能参与胰岛素介导的葡萄糖转运刺激作用这一观点一致。它们还表明，去神经支配诱导的葡萄糖转运胰岛素抵抗可能反映了参与信号级联反应的某些DAG生成受损。
