Barriocanal L A, Borthwick A C, Stewart M, Wells A, Hurel S J, Yeaman S J, Taylor R
Department of Medicine, University of Newcastle, Newcastle upon Tyne, UK.
Diabet Med. 1995 Dec;12(12):1110-5. doi: 10.1111/j.1464-5491.1995.tb00429.x.
Previous studies have established that activation of muscle glycogen synthase (GS) is abnormal in non-insulin-dependent diabetes mellitus (NIDDM). Insulin-mediated activation of GS depends upon protein phosphatase-1 (PP1), which dephosphorylates the relevant sites of GS. In order to determine whether defects in PP1 activation cause subnormal activation of GS or whether PP1 activation itself is normal, we administered a short insulin infusion to 8 NIDDM subjects and 8 healthy controls matched for gender, age, and body mass index (BMI). GS fractional activity and PP1 activity were determined in biopsies taken from the gastrocnemius muscle before and after 60 min insulin infusion (0.1 U kg h-1). In the NIDDM group, muscle GS fractional activity was 6.8 +/- 1.6 and 10.0 +/- 1.5% (mean +/- SEM) (p = 0.11) before and after insulin infusion. In the control group, muscle GS fractional activity increased from 7.3 +/- 2.0 to 13.3 +/- 2.7% (p < 0.02). PP1 activity had returned towards basal levels after insulin infusion; NIDDM group 156 +/- 24.7 to 184.1 +/- 28.1 U mg-1; control group 220.8 +/- 30.1 to 233.8 +/- 29.8 U mg-1. In the NIDDM group there was a positive correlation between the increases in GS fractional activity and PP1 activity following insulin stimulation r = 0.77; p < 0.025). These data indicate that in vivo insulin-dependent activation of muscle PP1 is transient in normal subjects but is delayed in NIDDM. The defect in GS activation in NIDDM is likely to be proximal to PP1 in the pathway of transmission of the insulin signal.
先前的研究已证实，非胰岛素依赖型糖尿病（NIDDM）患者肌肉糖原合酶（GS）的激活存在异常。胰岛素介导的GS激活依赖于蛋白磷酸酶-1（PP1），它使GS的相关位点去磷酸化。为了确定PP1激活缺陷是否导致GS激活不足，或者PP1激活本身是否正常，我们对8名NIDDM患者和8名性别、年龄及体重指数（BMI）相匹配的健康对照者进行了短时间胰岛素输注。在胰岛素输注（0.1 U·kg·h-1）60分钟前后，从腓肠肌活检组织中测定GS的分数活性和PP1活性。在NIDDM组，胰岛素输注前后肌肉GS分数活性分别为6.8±1.6%和10.0±1.5%（平均值±标准误）（p = 0.11）。在对照组，肌肉GS分数活性从7.3±2.0%增加到13.3±2.7%（p < 0.02）。胰岛素输注后PP1活性恢复至基础水平；NIDDM组从156±24.7 U·mg-1变为184.1±28.1 U·mg-1；对照组从220.8±30.1 U·mg-1变为233.8±29.8 U·mg-1。在NIDDM组，胰岛素刺激后GS分数活性增加与PP1活性增加之间存在正相关（r = 0.77；p < 0.025）。这些数据表明，正常受试者体内胰岛素依赖的肌肉PP1激活是短暂的，而在NIDDM患者中则延迟。NIDDM中GS激活缺陷可能在胰岛素信号传导途径中位于PP1的上游。
