Kobayashi S, Fujihara M, Hoshino N, Kimura I, Kimura M
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
Endocrinol Jpn. 1989 Dec;36(6):833-44. doi: 10.1507/endocrj1954.36.833.
The effect of a diabetic state in the diabetic KK-CAy mouse on calcium activated neutral proteinase (CANP) of hind-limb skeletal muscles was investigated. In the diabetic state, there was an increased sensitivity to activation of CANP by calcium (Ca). In addition, there was an enhancement of maximal activity of the enzyme. The effect was induced by secondary modification of the diabetic state, but not genetical factors. Several lines of evidence suggest that the CANP is responsible for 92 K dalton protein in diabetic skeletal muscles. Among the evidence are the following: a) The 92 K band in the diabetic muscles was lower than in the prediabetic mouse and restored by the addition of 2 mM EDTA and 2 mM EGTA. b) The band was reduced by increasing the Ca content and neutral pH in the non-diabetic normal muscles. c) E-64-C, a CANP inhibitor, restored the 92 K component reduced by the diabetic state. Since the band in denervated muscles was not changed by the Ca chelating agents, the reduction of the band in the diabetic muscles is related with musculotrophic factors, not diabetic neuropathy. These results suggest that diabetic amyotrophy may be regarded as a phenomenon linked to an increase in intracellular Ca ions and an increase in CANP activity.
研究了糖尿病KK - CAy小鼠的糖尿病状态对后肢骨骼肌钙激活中性蛋白酶（CANP）的影响。在糖尿病状态下，钙（Ca）对CANP激活的敏感性增加。此外，该酶的最大活性增强。这种作用是由糖尿病状态的继发性改变引起的，而非遗传因素。几条证据表明CANP与糖尿病骨骼肌中的92K道尔顿蛋白有关。这些证据如下：a）糖尿病肌肉中的92K条带低于糖尿病前期小鼠，添加2 mM乙二胺四乙酸（EDTA）和2 mM乙二醇双乙醚二胺四乙酸（EGTA）后恢复。b）通过增加非糖尿病正常肌肉中的钙含量和中性pH值，该条带减少。c）CANP抑制剂E - 64 - C恢复了因糖尿病状态而减少的92K成分。由于失神经肌肉中的条带不受钙螯合剂影响，糖尿病肌肉中条带的减少与肌肉营养因子有关，而非糖尿病神经病变。这些结果表明糖尿病性肌萎缩可被视为一种与细胞内钙离子增加和CANP活性增加相关的现象。
