胰島素補充療法為糖尿病的治療帶來了一片曙光，但是胰島素阻抗 (Insulin Resistance) 的問題接踵而來。因此，研究如何增加胰島素敏感度 (Insulin Sensitivity) 乃是當代醫學重要的課題。另一方面類固醇常廣泛運用在臨床的治療，而類固醇的濫用易造成胰島素阻抗的產生。運用大量類固醇誘發胰島素阻抗，恰可模擬此一臨床常見病態，尋找有效防治之道。 本研究希望運用大量類固醇快速建立胰島素阻抗之動物模式，並且運用胰島素挑戰試驗 (Insulin challenge test，ICT)、葡萄糖耐量試驗 (Glucose tolerance test，GTT) 及胰島素阻抗指標 (HOMA Index)，進行類固醇誘發胰島素阻抗模式的評估。另一方面, 經由文獻回顧發現 Glucocorticoid 能減少 GLUT4 訊息蛋白轉移到細胞膜，增加血中 Free fatty acid 之濃度，進而抑制肌肉對胰島素刺激之血糖攝取。因此，我們一方面檢測血中游離脂肪酸 (Free Fatty Acid, FFA) 之含量。探討類固醇誘發胰島素阻抗之機轉，此一模式建立之後，可藉由骨骼肌中胰島素訊息蛋白IRS-1、Akt、 IP3K、GLUT4的變化探討電針改善類固醇引發的胰島素阻抗之作用機轉。 另有研究顯示電針能降低 FFA之含量。快速模式建立之後，可藉由FFA的分析，探討電針改善類固醇引發的胰島素阻抗之作用機轉。可藉由檢測血中 FFA的含量及骨骼肌中胰島素訊息蛋白IRS-1、IP3K、Akt、GLUT4受電針之影響，使電針改善胰島素阻抗性的作用機轉更為完整。藉以闡明電針改善類固醇引發的大白鼠胰島素阻抗之作用機轉。 結果顯示 : 短期運用大量類固醇可成功誘發胰島素阻抗性的產生。 使用大量類固醇後，實驗組的大白鼠比對照組大白鼠在葡萄糖耐量試驗 (GTT) 及胰島素阻抗指標 (HOMA Index) 上皆有顯著上升。另一方面檢測血中游離脂肪酸之含量，實驗組的大白鼠在30及60分鐘皆比對照組的大白鼠有顯著上升。進一步探討骨骼肌中胰島素訊息蛋白發現大量的類固醇可抑制骨骼肌中IRS-1、IP3K的含量，GLUT4似無明顯變化，而電針似可回復IRS-1的作用，唯樣本數過少仍須進一步實驗證實此一現象。 結論 : 利用此一快速模式之建立，成功縮短胰島素阻抗性誘發時間，節省研究時間與成本，進一步能快速運用在中醫藥及針灸增加胰島素敏感度之研究，藉以尋找有效的胰島素增敏方法，進一步提供臨床使用，嘉惠病患。; Objective: Glucocorticoids impair insulin sensitivity due to steroid increase triglyceride and free fatty acid level. In liver and muscle, steroid treatment result in reduction of insulin stimulated IRS-1 associated PI-3 kinase.This study will creat a fast animal model of insulin resistance by way of large amount of prednisolone. Furthermore, electroacupuncture were interventioned in attempting to reverse this phenomenon and increase insulin signal proteins for improving insulin resistance. Design and Methods: Male Wistar rats aged 8-10 weeks with intraperitoneal injection of prednisolone (40mg/kg) were used as models of insulin resistance rats. After injection of prednisolone for 30、60 and 90 mins, blood samples were assayed on plasma glucose and insulin levels for the calculation of HOMA index. IVGTT and FFA level change were proceeded to evaluate insulin resistance. Furthermore, skeletal muscle was isolated to investigate insulin signaling protein (IRS-1, PI-3 kinase, Akt and GLUT-4 ) amount for evaluate insulin resistance. Results: A marked increase of HOMA index at 30 and 60 mins by large amount of prednisolone induced Wistar rat than control. Under IVGTT was proceeding, marked lower plasma glucose were found at 30 and 60 mins in normal Wistar rats than steroid induced Wistar rats. Further more, plasma FFA level were increased in steroid induced Wistar rats than normal rats. This discovery just can illustrate the mechanism of insulin resistance induced by large amount steroid. In the other hand, skeletal muscle was isolated to investigate the effect of steroid on insulin signals. There were trend of reduced amount of insulin signals (IRS-1, PI3-kinase) due to large amount steroid. Electroacupuncture may improve insulin resistance by reverse this phenomenon. More data will be needed to confirm this result about the change of insulin signal protein. Conclusion: These results suggest that single large dose of prednisolone can successfully set an animal model of insulin resistance.
