Benelli C, Lopez S, Desbuquois B, Achagiotis C
Institut National de le Santé et de la Recherche Médicale, Unité 30, Hôpital des Enfants Malades, Paris, France.
Diabetes. 1988 Jun;37(6):717-22. doi: 10.2337/diab.37.6.717.
Acute insulin treatment in rats has recently been shown to cause a rapid increase in liver low-Km cAMP phosphodiesterase (PDE) activity, which selectively affects Golgi fractions. To assess the physiological significance of this observation, the cAMP PDE activity associated with liver Golgi fractions has been measured in genetically obese Zucker rats, which spontaneously develop hyperinsulinemia, in rats receiving a continuous infusion of insulin, and in rats treated with anti-insulin serum. In genetically obese Zucker rats, a significant increase in Golgi-associated cAMP PDE relative to age-matched lean animals occurred after 3 wk, coinciding with the development of hyperinsulinemia. This change was maximal at 5-8 wk and affected the light (Gl) and intermediate (Gi) Golgi fractions (100-110% increase) to a greater extent than the heavy (Gh) fraction (30% increase). After 7 wk, despite the further increase in insulinemia, the increase in Golgi-associated cAMP PDE became progressively less marked, and at 18 wk it was no longer detectable except in Gh, suggesting the development of a hepatic insulin resistance. Infusion of insulin through chronically implanted intracardiac catheters led to a 30-50% increase in Golgi-associated cAMP PDE, which occurred earlier in Gi (3 h) than in Gh (7 h) and persisted for greater than 96 h. Injection of anti-insulin serum led to a 30-50% decrease in Golgi-associated cAMP PDE, which occurred sequentially in Gl (5 min), Gi (15 min), and Gh (30 min) and affected predominantly Gl and Gh. These results suggest that the cAMP PDE associated with Golgi fractions is a physiological effector of plasma insulin in vivo.
最近有研究表明，对大鼠进行急性胰岛素治疗会导致肝脏低 Km cAMP 磷酸二酯酶（PDE）活性迅速增加，这种酶选择性地影响高尔基体部分。为了评估这一观察结果的生理意义，我们测定了遗传性肥胖 Zucker 大鼠（其会自发出现高胰岛素血症）、接受胰岛素持续输注的大鼠以及用抗胰岛素血清治疗的大鼠肝脏高尔基体部分相关的 cAMP PDE 活性。在遗传性肥胖 Zucker 大鼠中，相对于年龄匹配的瘦鼠，3 周后高尔基体相关的 cAMP PDE 显著增加，这与高胰岛素血症的发生相吻合。这种变化在 5 - 8 周时达到最大，对轻（Gl）和中（Gi）高尔基体部分的影响（增加 100 - 110%）比对重（Gh）部分的影响（增加 30%）更大。7 周后，尽管胰岛素血症进一步增加，但高尔基体相关的 cAMP PDE 的增加逐渐不明显，到 18 周时，除了 Gh 部分外，其他部分已无法检测到，这表明出现了肝脏胰岛素抵抗。通过长期植入的心内导管输注胰岛素会导致高尔基体相关的 cAMP PDE 增加 30 - 50%，Gi 部分（3 小时）比 Gh 部分（7 小时）更早出现增加，且持续超过 96 小时。注射抗胰岛素血清会导致高尔基体相关的 cAMP PDE 降低 30 - 50%，依次在 Gl（5 分钟）、Gi（15 分钟）和 Gh（30 分钟）出现降低，主要影响 Gl 和 Gh。这些结果表明，与高尔基体部分相关的 cAMP PDE 是体内血浆胰岛素的一种生理效应器。
