REGULATION OF LIVER-CELL VOLUME AND PROTEOLYSIS BY GLUCAGON AND INSULIN
REGULATION OF LIVER-CELL VOLUME AND PROTEOLYSIS BY GLUCAGON AND INSULIN
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DOI：
10.1042/bj2780771
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发表时间：
1991-09-15
影响因子：
4.1
通讯作者：
HAUSSINGER, D
中科院分区：
文献类型：
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作者：
DAHL, SV;HALLBRUCKER, C;HAUSSINGER, D
研究了胰岛素和胰高血糖素对大鼠离体肝细胞体积和蛋白水解的影响。通过腹腔注射[H-3]亮氨酸预标记的大鼠体内单次灌注肝脏释放[H-3]亮氨酸来评估蛋白质水解率。通过同时加入[H-3]菊粉和[C-14]尿素的冲刷曲线测定细胞内的水空间。在正常渗透（305 mosM）对照灌注中，细胞内水空间为548 +/- 10 μ -l/g湿质量（n = 44），在低渗暴露（225 mosM）后，细胞内水空间增加了16.5 +/- 2.6% (n = 6)，即85 +/- 14 μ -l/g。胰高血糖素（0.1 μ m）使细胞内水空间减少了17.4% (n = 4)，而胰岛素（35 nM）使细胞内水空间增加了9.3 +/- 1.4% （n = 15）。此外，在分离的大鼠肝细胞悬液中，胰岛素（100 nM）引起细胞肿胀10.7 +/- 1.8% (n = 16)，胰高血糖素完全逆转。在灌注的肝脏中，胰岛素诱导的细胞肿胀伴随着肝脏净K+摄取（4.5 +/- 0.2 μ mol/g）和蛋白质水解抑制21 +/- 2% (n = 12)；进一步添加胰高血糖素导致净K+释放3.8 +/- 0.2 μ mol/g (n = 7)，并完全逆转胰岛素对细胞体积和蛋白水解的影响。同样，胰岛素诱导的细胞肿胀和蛋白水解抑制被高渗（385 mosM）细胞收缩完全拮抗。此外，低渗透暴露或氨基酸添加后的细胞肿胀和蛋白水解抑制被胰高血糖素诱导的细胞收缩逆转。无论胰岛素、胰高血糖素或异渗透暴露是否改变细胞体积，细胞肿胀程度与蛋白水解抑制之间都存在密切关系。数据表明，胰高血糖素和胰岛素是肝细胞体积的有效调节剂，至少部分是通过改变细胞K+平衡，它们对肝蛋白水解的相反作用在很大程度上可以通过对细胞体积的相反作用来解释。据推测，激素诱导的细胞体积的改变可能代表了一个重要的，尚未认识到的机制，介导激素对代谢的影响。
The effects of insulin and glucagon on liver cell volume and proteolysis were studied in isolated perfused rat liver. The rate of proteolysis was assessed as [H-3]leucine release from single-pass-perfused livers from rats which had been prelabelled in vivo by intraperitoneal injection of [H-3]leucine. The intracellular water space was determined from the wash-out profiles of simultaneously added [H-3]inulin and [C-14]urea. In normo-osmotic (305 mosM) control perfusions the intracellular water space was 548 +/- 10-mu-l/g wet mass (n = 44) and was increased by 16.5 +/- 2.6% (n = 6), i.e. by 85 +/- 14-mu-l/g, after hypoosmotic exposure (225 mosM). Glucagon (0.1-mu-M) decreased the intracellular water space by 17 +/- 4% (n = 4), whereas insulin (35 nM) increased the intracellular water space by 9.3 +/- 1.4% (n = 15). Also, in isolated rat hepatocyte suspensions insulin (100 nM) caused cell swelling by 10.7 +/- 1.8% (n = 16), which was fully reversed by glucagon. In perfused liver, insulin-induced cell swelling was accompanied by a hepatic net K+ uptake (4.5 +/- 0.2-mu-mol/g) and an inhibition of proteolysis by 21 +/- 2% (n = 12); further addition of glucagon led to a net K+ release of 3.8 +/- 0.2-mu-mol/g (n = 7) and fully reversed the insulin effects on both cell volume and proteolysis. Similarly, insulin-induced cell swelling and inhibition of proteolysis were completely antagonized by hyperosmotic (385 mosM) cell shrinkage. Furthermore, cell swelling and inhibition of proteolysis after hypo-osmotic exposure or amino acid addition were reversed by glucagon-induced cell shrinkage. There was a close relationship between the extent of cell swelling and the inhibition of proteolysis, regardless of whether cell volume was modified by insulin, glucagon or aniso-osmotic exposure. The data show that glucagon and insulin are potent modulators of liver cell volume, at least in part by alterations of cellular K+ balance, and that their opposing effects on hepatic proteolysis can largely be explained by opposing effects on cell volume. It is hypothesized that hormone-induced alterations of cell volume may represent an important, not yet recognized, mechanism mediating hormonal effects on metabolism.