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惡性神經膠質瘤是最常見的 primary brain tumor 腫瘤之一，其癌化的
成因目前還不清楚。胰島素存在於中樞神經系統中，它除了可以促進神經
細胞的生長與發育，調節食物的攝取，也可以當作神經調節因子。本研究
的主題是探討胰島素對神經膠質瘤之生理代謝上的調節功能；針對細胞內
蛋白質磷酸化，protein kinase C，細胞形態 ，細胞生長等性質的影響
比較與正常細胞之差異。當養在含胰島素培養基時，膠質瘤細胞的細胞
內 Ser/Thr 磷酸化反應呈現低磷酸化反應的狀態；但是，正常的膠質細
胞在同樣的條件之下卻會增強其細胞內磷酸化活性。本研究證實這樣的現
象具有專一性。胰島素可造成膠質瘤細胞磷酸化活性下降的現象在十分鐘
的刺激下即有反應，大約到五小時後，可以達到最低狀態。而正常的膠質
細胞也大致依循相似的作用時間模式來增強其細胞磷酸化活性。這種磷酸
化的調節是隨著胰島素的劑量而變的，大約於 500 ng/ml 的胰島素濃度
下，膠質瘤細胞內磷酸化活性便明顯的受到抑制。類胰島素生長因子—
Ⅰ 在實驗劑量下，無法像胰島素那樣造成膠質瘤細胞磷酸化活性的下降
。顯示這可能是一種胰島素專一的反應。這種胰島素所引發的磷酸化活性
的改變會受到轉譯抑制物 actinomycin D 和轉錄抑制物 cycloheximide
的抑制。胰島素對細胞生長速度的影響，會隨著胎牛血清濃度的增加而有
部份差異。養在含有胰島素培養基下的膠質瘤細胞長得比不含胰島素的膠
質瘤細來得快；但是胰島素會減緩膠質細胞的生長速度。不過，胰島素並
不會造成膠質瘤細胞和膠質細胞形態上的改變。此外，胰島素也會影響膠
質瘤細胞和膠質細胞的 PKC 活性。在胰島素的刺激下，膠質瘤細胞的總
PKC 活性都是增強，而膠質細胞的總 PKC 活性卻減弱了。以西方點墨法
(Western-blotting) 偵測 PKC 次種類蛋白質的表現，發現正常的膠質細
胞不管是膜部份或細胞質部份，也不論有沒有胰島素的刺激都沒有PKC-a,
b,d,g,e 次種類蛋白質的表現。而膠質瘤細胞之 PKC-a,b,d 都只表現在
細胞質部份。胰島素刺激之後，會使原先在膜部份有表現的 PKC-e 和只
表現在細胞質部份的 PKC-g 都消失了；即胰島素似乎能降低 (down-
regulate) PKC-g 和 PKC-e 蛋白質的表現。
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Malignant glioma is one of the most common tumors affecting
human central nervous system (CNS). Insulin existing in the CNS
can promote the growth of neuron and acts as a neuromodulator.
When grew in insulin-containing medium, the Ser/Thr
phosphorylation was low in gliomas, but was high in normal
glial cells. In gliomas, the descend of phosphorylation
activity by insulin was detected in the ten minutes and reached
to minimum after five hours. The raise of phosphorylation
activity in glial cells by insulin followed a similar reaction
time mode. The regulation of phosphorylation by insulin was
dose-dependent; significant inhibition in gliomas was detected
as low as 500 ng/ml of insulin. IGF-I could notsuppress the
phosphorylation activity in gliomas. The change of
phosphorylation activity induced by insulin could be partly
inhibited by actinomycin D and cycloheximide. The cell growth
rate was more affected by insulin along with the increase of
concentration of fetal calf serum. Glioma cells cultured in
insulin-containing medium grew more faster than those cultured
in insulin-free medium. On the contrary, insulin reduced the
growth rate of glial cells. Insulin treatment did not lead
morphological change of both glioma and glial cells. After
insulin stimulation, the total PKC activities of gliomas were
increased, but that of glial cells were decreased. Using
Western-blotting, the PKC-a, b, d, g, and e subspecies proteins
in glial cells were not detected regardless with or without
insulin stimulation. The PKC-a, b, and d were constitutively
expressed in the cytosolic fraction of gliomas. Insulin would
down-regulate the expression of PKC-e in the membrane fraction
and PKC-g in the cytosolic fraction of gliomas.
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