Salsolinol對第二型糖尿病小鼠降血糖作用之研究

根據中華民國衛生福利部的統計，新陳代謝疾病—糖尿病位居國人十大死因的第五位，其中又以第二型糖尿病患者是較為普見的，而且不僅僅台灣，糖尿病同時也是全球十大死因之一，常會導致神經以及心血管相關的併發症，嚴重的話還可能導致心肌梗塞等等的致命性併發症。且由於人口的增加、邁入老年化社會、都市化、肥胖人數增加、運動減少以及不健康的飲食習慣，導致全球糖尿病患者數預計在西元2025年會達到3億人口。使得開發新的降血糖藥物成為了全球急需處理的問題之一。 Salsolinol，是屬於生物鹼類﹝alkaloid﹞的多巴胺﹝dopamine﹞衍生物，在人體內就有內生性的salsolinol存在，且也可以透過食物的攝取像是香蕉、起司、紅酒等等來獲得，此成分被發現存在於一種具降血糖作用之植物水萃成分中，salsolinol能顯著活化培養細胞﹝C2C12﹞磷酸化腺苷酸依賴蛋白激酶﹝AMPK﹞的表現。在動物體之降血糖作用評估中，發現salsolinol能有效地改善飲食誘發第二型糖尿病小鼠的禁食血糖亦能有效地改善口服葡萄糖耐受性試驗中血糖提升之現象。此外，急性治療試驗中也發現salsolinol能顯著增加胰島素的釋放。另外，在飲食誘發第二型糖尿病小鼠的實驗模式中，每天口服給予10 mg/kg的salsolinol，在經過14天治療後，能顯著的減少血液中的總膽固醇、三酸甘油酯且能有效地增加肝臟以及骨骼肌處之肝醣合成；在脂肪組織部分，salsolinol組之脂肪細胞尺寸以及附睪脂肪占體重百分比都明顯小於負對照組。因此，基於本篇實驗所發現，我們可以知道salsolinol的降血糖作用可能和磷酸化腺苷酸依賴蛋白激酶﹝AMPK﹞的活化以及促進胰島素釋放有關，雖然salsolinol的詳細的降血糖機制目前尚未明瞭，但由本篇研究的結果可以看到salsolinol具有優秀的潛力在未來能開發成為新的降血糖藥物。

關鍵字

salsolinol ； antihyperglycemia ； diabetic mice ； AMPK ； T2DM

並列摘要

Type 2 diabetes mellitus ( DM ) is a chronic metabolic disorder , whose prevalence has been increasing dramatically all over the world due to population growth , increase in aging population , urbanization and unhealthy diet in high-caloric food . Besides , DM also ranked in the top ten causes of mortality , often leads to neurological complications , myocardial infraction and vascular complications . Therefore , the development of new pharmacological approaches to effectively prevent and treat this metabolic syndrome is of crucial importance . Salsolinol , an alkolid derivate of dopamine from a herbal plant ( GYT 067 ) , significantly stimulated the phosphorylation on AMPK in C2C12 cells . Salsolinol ( 10 mg/kg ) significantly attenuated the fasting plasma glucose and the elevation of plasma glucose induced by an OGTT in diet-induced type 2 diabetic mice . Besides , the secretion of insulin was significantly increased after the acute treatment with salsolinol . Moreover , after 2-week treatment , salsolinol produced a significant reduction in plasma total cholesterol , plasma triglycerides , adipocyte size and the ratio of epididymal fat weight / body weight . Also , salsolinol significantly increased glycogen synthesis both in skeletal muscle and liver after treatment with salsolinol daily for 2 weeks . Therefore , based on our present study , we conclude that the mechanisms of salsolinol in the hypoglycemic effect may be related to the stimulation of AMPK and increase of insulin release . Although the clear mechanisms for the hypoglycemic activities remain to be determined , the well-characterized antidiabetic effects shown in our study suggest that salsolinol can be a potential agent for the treatment of diabetes in the future .

並列關鍵字

salsolinol ； antihyperglycemia ； diabetic mice ； AMPK ； T2DM

參考文獻

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Salsolinol對第二型糖尿病小鼠降血糖作用之研究

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