KINETICS AND SPECIFICITY OF INSULIN UPTAKE FROM PLASMA INTO CEREBROSPINAL-FLUID
KINETICS AND SPECIFICITY OF INSULIN UPTAKE FROM PLASMA INTO CEREBROSPINAL-FLUID
复制标题
DOI：
10.1152/ajpendo.1990.259.3.e378
复制
发表时间：
1990-09-01
影响因子：
--
通讯作者：
PORTE, D
中科院分区：
文献类型：
--
作者：
SCHWARTZ, MW;SIPOLS, A;PORTE, D
为了表征血浆中胰岛素水平与脑脊液（CSF）中胰岛素水平之间的关系，我们研究了CSF从血浆中摄取胰岛素的动力学和CSF隔室内胰岛素的周转。正常血糖高胰岛素血症的持续生理水平（血浆胰岛素约为0.000000）。500 pM）在第1小时内没有改变CSF胰岛素水平，但到90分钟时观察到显著增加（P < 0.01）。在分级高胰岛素钳夹期间（平均血浆胰岛素apprx. 500- 15，000 pM），CSF胰岛素以剂量依赖性方式升高。这种升高的特征是初始延迟，随后在接下来的150分钟内持续增加。我们还发现，在短暂的、高剂量静脉内胰岛素输注后，CSF胰岛素的T1/2为143 ± 1.5。7 min（平均值±）SE; n = 4），类似于通过大量流动的CSF周转。为了检测CSF从血浆中摄取胰岛素的特异性，我们将静脉输注胰岛素期间的这种摄取与胰岛素原（一种对胰岛素受体亲和力降低的肽）的摄取进行了比较。我们观察到在180分钟内CSF胰岛素原水平的显著较低的增量（13.6 ± 0.01）。1.6 pM;平均值±. SE; n = 4）与胰岛素（22.4 . ±. 0.6 pM; n = 4; P < 0.01），尽管血浆胰岛素原水平高于胰岛素（1，890. ±.二百八十七对一千二百八十三。192 pM; P < 0.001）。当校正血浆水平的差异时，胰岛素的摄取是胰岛素原的5倍。综上所述，这些观察结果表明，尽管最初延迟，但血浆胰岛素的生理性增加导致CSF胰岛素水平显著升高，并且与CSF中胰岛素摄取部分通过胰岛素特异性机制发生的假设一致。
To characterize the relationship between insulin levels in plasma and those in cerebrospinal fluid (CSF), we studied the kinetics of both the uptake of insulin into CSF from plasma and the turnover of insulin within the CSF compartment. Sustained physiological levels of euglycenic hyperinsulinemia (plasma insulin .apprx. 500 pM) did not alter CSF insulin levels within the 1st h, but by 90 min a significant increase was observed (P < 0.01). During graded hyperinsulinemic clamps (mean plasma insulin .apprx. 500-15,000 pM), CSF insulin rose in a dose-depndent fashion. This rise was characterized by an initial delay followed by a continuous increase for the next 150 min. We also found that after brief, high-dose intravenous insulin infusions, the T1/2 of CSF insulin was 143 .+-. 7 min (mean .+-. SE; n = 4), similar to that of CSF turnover by bulk flow. To test the specificity of CSF insulin uptake from plasma, we compared this uptake during intravenous insulin infusions with that of proinsulin, a peptide with reduced affinity for the insulin receptor. We observed a significantly lower increment of CSF proinsulin levels over 180 min (13.6 .+-. 1.6 pM; means .+-. SE; n = 4) compared with that of insulin (22.4 .+-. 0.6 pM; n = 4; P < 0.01), despite plasma proinsulin levels higher than insulin (1,890 .+-. 287 vs. 1,283 .+-. 192 pM; P < 0.001). When corrected for the difference in plasma levels, the uptake of insulin was fivefold greater than that of proinsulin. Taken together, these observations indicate that, despite an initial delay, physiological increases in plasma insulin produce significant elevations of CSF insulin levels and are consistent with the hypothesis that insulin uptake into CSF occurs in part via a mechanism with specificity for insulin.