蛹蟲草水萃物之降血糖機制

糖尿病會有許多的併發症，以致於造成殘疾或危及生命。先前的研究發現蛹蟲草有降血糖的功能，但是其真正的機轉仍是不明。此研究的目的便是要釐清蛹蟲草的降血糖機轉。本研究分成兩個部分：第一部分為正常的大鼠以蛹蟲草的水萃取物餵食。最佳的降血糖劑量是10 mg/kg，此劑量比100 mg/kg有更好的效果，所以之後的治療劑量都是10 mg/kg。對於正常大鼠，蛹蟲草餵食30分鐘後可以降低血糖達21.0%，同時可增加54.5%胰島素分泌。如果大鼠先給予腹膜內注射0.1 mg/kg阿托品(atropine)以阻斷膽鹼神經，則蛹蟲草之降血糖與增加胰島素分泌的效果就消失。分析胰島素訊息蛋白時，發現在餵食蛹蟲草後，胰島素受體受質-1 (insulin receptor substrate 1, IRS-1)與葡萄糖運送子-4 (glucose transporter 4, GLUT-4)會增加(與肌動蛋白的比值分別為餵食食鹽水的3.63與2.64倍)。相同的，這些胰島素訊息蛋白的增加也被阿托品所阻斷，同樣的阻斷作用，也可見於事先注射了半膽鹼-3(hemicholinium-3)的大鼠實驗。第二部分以注射鏈佐黴素(streptozotocin)而誘發糖尿病的大鼠為對象，餵食蛹蟲草可以降低血糖7.2%，但若餵食食鹽水只有降低1.5%。胰島素受體受質-1在蛹蟲草增加2.9倍，食鹽水組只有0.8倍。葡萄糖運送子-4則於蛹蟲草與食鹽水組分別為1.7與0.6倍。若大鼠先以阿托品注射，則蛹蟲草組的降血糖及胰島素訊息蛋白的增加也會被阻斷。總結而言，蛹蟲草刺激正常大鼠的胰臟分泌胰島素，繼而活化更多肌肉細胞內的胰島素訊息蛋白使血糖下降。在鏈佐黴素誘發糖尿病的大鼠，因為胰島素而降血糖的機制幾乎不存在，但蛹蟲草仍可增加胰島素訊息蛋白並降血糖。兩種動物模型的有效反應，都可被副交感神經拮抗劑所阻斷。所以，蛹蟲草能夠降血糖的機轉可能為啟動膽鹼神經而增加胰島素分泌以及非胰島素依賴的降血糖作用。

關鍵字

蛹蟲草；糖尿病；降血糖機轉；抗膽鹼作用

並列摘要

There are many diabetic complications which induce patients’ disability or loss their life. Previous study found Cordyceps militaris (CM) had hypoglycemic effect, yet the actual mechanism remains unclear. We would like to explore the mechanism of CM’s hypoglycemia. The experiments were separated into two portions. In the first one, aqueous extracts of CM was feeding to the normal Wistar rats. The optimal dose of CM for lowering serum glucose was tested first and found that 10 mg/kg CM had a better hypoglycemic effect than a higher dose (100 mg/kg). Such optimal dose was used in following experiments. In the normal rats, CM decreased plasma glucose by 21.0% and induced additional insulin secretion by 54.5% at 30 minute. Additionally, atropine 0.1 mg/kg was injected intraperitoneally as an antagonist to the cholinergic nerve. The hypoglycemic effects of CM vanished and the enhanced insulin secretion was also blocked. In the assay of insulin signaling proteins, a significant rise in the insulin receptor substrate 1 (IRS-1) and glucose transporter 4 (GLUT-4) were found in the rats after being fed CM (3.63- and 2.64-fold in comparison with fed saline). However, these rising signaling proteins were blocked by the atropine. And the same responses were found in the hemicholinium-3 (5μg/kg intraperitoneally) pre-treated rats. The second portion of experiments was performed to the streptozotocin (STZ)- induced diabetic rats. Blood glucose decreased 7.2% in the CM group but only 1.5% in the control group. The IRS-1 signal was 2.9-fold in the CM group but only 0.8-fold in the control group. In GLUT-4 signal, it was 1.7- vs. 0.6-fold, respectively. However, atropine injection made CM-induced hypoglycemia or elevation of IRS-1 and GLUT-4 not significant. In conclusion, CM stimulates the pancreas of normal rats to secrete additional insulin and activates the insulin signaling proteins via the binding of more insulin to its receptors in the myocyte. In the STZ-induced diabetic rats, the influence of insulin hypoglycemic effect was little, but CM still had the effect of activating insulin signaling proteins in the myocytes. Both reactions were blocked by anti-cholinergic agents. Taken together, the possible mechanisms of CM-induced hypoglycemia in both types of animal models were the induction of insulin secretion and non-insulin dependent hypoglycemic effect mainly triggered by activation of the cholinergic nerve.

並列關鍵字

Cordyceps militaris ； diabetes mellitus ； hypoglycemic mechanism ； anticholinergic effect

參考文獻

31. 林世崇. 糖尿病治療的新策略. 台灣醫界 2010; 53:16-23.

39. 劉松臻, 王朝弘 and 簡銘男. 長效型胰島素類似物在第2型糖尿病人的應用. 內科學誌 2010; 21:109-116.

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2. American Diabetes Association. Standards of Medical Care in Diabetes—2011. Diabetes Care 2011; 34, supplement 1:S11-S61.

3. American Diabetes Association. Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 2010; 33, supplement 1:S62-69.

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蛹蟲草水萃物之降血糖機制

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