Frier B M, Saudek C D
J Clin Endocrinol Metab. 1979 Dec;49(6):824-9. doi: 10.1210/jcem-49-6-824.
The turnover of isotopically labeled squalene formed in plasma from [14C]mevalonate has been used to measure cholesterol synthesis in diabetics over a 7-h period. Five patients were studied while in poor diabetic control (mean daytime glycemia, 349 mg/dl) and at a later date once improved control was established by multiple daily insulin injections (mean glycemia, 175 mg/dl). This degree of diabetic control resulted in an increase in the fractional conversion of [14C]mevalonic acid to [14C]squalene from 55.2 +/- 1% to 67.5 +/- 4% (P less than 0.025). These data together with the area under the squalene specific activity curve yeild an estimated rate of cholesterol synthesis based on the likely assumption that mevalonate pool size did not decrease. Insulinization increased this calculated mean rate of cholesterol synthesis from 961 +/- 151 to 1206 +/- 223 mg/day (P less than 0.025). The use of squalene kinetics to evaluate changes in cholesterol synthesis deserves further study, particularly in metabolically unstable states such as diabetes in which conventional methods for measuring cholesterol synthesis are difficult to apply and to interpret.
利用[14C]甲羟戊酸在血浆中形成的同位素标记角鲨烯的周转率，在7小时内测量糖尿病患者的胆固醇合成。对5名患者进行了研究，一次是在糖尿病控制不佳时（白天平均血糖为349mg/dl），另一次是在后来通过每日多次注射胰岛素建立了更好的控制之后（平均血糖为175mg/dl）。这种糖尿病控制程度使得[14C]甲羟戊酸向[14C]角鲨烯的分数转化率从55.2±1%增加到67.5±4%（P<0.025）。这些数据与角鲨烯比活性曲线下的面积一起，基于甲羟戊酸池大小没有减少这一可能的假设，得出了胆固醇合成的估计速率。胰岛素治疗使计算出的胆固醇合成平均速率从961±151mg/天增加到1206±223mg/天（P<0.025）。利用角鲨烯动力学来评估胆固醇合成的变化值得进一步研究，特别是在代谢不稳定状态如糖尿病中，在这种状态下，测量胆固醇合成的传统方法难以应用和解释。
