隨著人口、工業發展與生產的需求增加，加上配合全球化趨勢，夜間輪班工作、熬夜加班等工作型態日益普及，人們夜間睡眠時間不足，造成睡眠剝奪的機會增加。研究指出，長期的睡眠剝奪會透過發炎反應造成多重器官損傷與血糖代謝問題，進而增加糖尿病風險，二甲雙胍是常用於高血糖與糖尿病的第一線藥物，可通過活化AMPK路徑達到降血糖與抗發炎的效果，由於目前睡眠剝奪後服用二甲雙胍藥物的影響仍未知，因此，本研究目的為探討二甲雙胍對睡眠剝奪造成之高血糖作用。睡眠剝奪採用改良式多平台法，實驗動物隨機分成五組，每組八隻，睡眠剝奪採一天剝奪一天休息方式為期30天，剝奪時間為早上7點至晚上7點。第一組為控制組；第二組為睡眠剝奪組；第三、四組為睡眠剝奪15天造成傷害後，再給予100和300 mg/kg/day p.o. 的二甲雙胍，至第30天；第五組為單獨給予300 mg/kg/day p.o.的二甲雙胍，從第15天開始餵食至第30天。全部測試小鼠在第31天犧牲，並採集血液、胰臟與肝臟進行後續分析。結果顯示，二甲雙胍可以減少胰臟與肝臟組織中介白質-1β和介白質-6的產生，並提升介白質-10的表現，且抑制發炎相關蛋白iNOS與NF-кB表現，降低血清中葡萄糖及GPT含量，增加胰臟與肝臟中葡萄糖運輸蛋白-2的表現，透過增加肝臟p-AMPK蛋白表現增加PPARγ、GCK、PFK-1及FBP-1表現；在組織切片中發現二甲雙胍無法恢復因睡眠剝奪造成的胰臟β細胞損失，且在單獨給予高劑量的情況下會增加血清中AMYL含量，並使胰臟組織變形且產生空洞。綜合上述，二甲雙胍可以經由增加糖解作用，來減緩因睡眠剝奪造成之高血糖現象及胰臟與肝臟組織的發炎情形，但服用高劑量二甲雙胍則可能會對胰臟與肝臟造成不良影響。

Sleep deprivation (SD) is increasing in the industrialized world. SD induces multiple organ injury and hyperglycemia via inflammatory response. SD also as a risk factor for type 2 diabetes. Metformin is used as a first-line drug for hyperglycemia and diabetes. However, the effect of metformin on SD-induced hyperglycemia, pancreatic and hepatic dysfunction have not been studied. The aim of the study was to investigate the effect of metformin on anti-hyperglycemia in SD mice. Mice were subjected to one day SD (7.00 am-7.00 pm) and sleep one day cycle for 15 cycles. Metformin (100 or 300 mg/kg/day p.o.) was administered from the 15th to the 30th day. Animals were killed on the 31st day. Metformin decreased liver and pancreatic IL-6, IL-1β, iNOS, NF-кB, serum GLU and GPT levels. It increased liver and pancreatic IL-10, GLUT2, liver p-AMPK, PPARγ, GCK, PFK-1 and FBP-1 levels, however it did not recovered the pancreatic cells histologically. In high dose metformin group, it increased the serum AMYL level and revealed islet atrophy, edge irregularities. In conclusion, metformin attenuated SD-induced hyperglycemia via PPARγ-GLUT2 glycolysis pathway and reduced inflammation, however high dose metformin may induce adverse effects in pancreas and liver.

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