益生菌相關代謝物對骨骼肌汲取葡萄糖能力之影響

Abstract

糖尿病(diabetes mellitus, DM)為一複雜的代謝性疾病，並常伴隨著許多併發症的產生，其與胰島素的分泌不足及作用異常有關。其中，第二型糖尿病約佔患者的90%，主要原因是胰島素阻抗(insulin resistance)所引起。因此，如何改善胰島素阻抗被認為是治療糖尿病的重要策略之一。近年來許多研究發現改變腸道菌相的組成，有助於改善肥胖與高血糖的現象，但也越來越多的研究指出腸道菌發酵後所產生的代謝產物(metabolites)可能是另一關鍵因素，並非只是單純改變腸道菌相的結果。因此，本研究採用已呈現胰島素阻抗症狀之L6骨骼肌細胞作為測試平台，針對不同代謝產物進行篩選，篩選出具有刺激骨骼肌細胞葡萄糖汲取能力之三種不同代謝產物，分別為共軛亞麻油酸(conjugated linoleic acid, CLA)、丁酸(butyric acid, BTY)以及亞精胺(spermidine, SPD)，並同時篩選出具有生產這些代謝產物能力之菌株，以及透過前驅物亞麻油酸(linoleic acid)及精胺酸(L-arginine)的添加來增加代謝產物的含量。最後，透過三種不同菌株(Bifidobacterium breve、Clostridium butyricum、Bacillus subtilis)的搭配組合，將其應用於黃豆粉固態發酵上，來進行代謝物組合物的發酵生產。結果顯示，經發酵生產後的產品其萃取物可有效提升骨骼肌細胞的葡萄糖汲取能力，可達到控制組 DMSO 的1.67倍，並且也顯著的優於胰島素的表現。因此，未來或許可望透過此產品組合物的應用，來對胰島素阻抗疾病發揮改善的效果。

Diabetes mellitus (DM) is a complex metabolic disease which often accompany with many complications. DM is caused by insufficient insulin secretion or resistance to insulin action on glucose uptake in peripheral tissues. It is estimated that about 90% of DM patients are type II diabetes worldwide and they are caused mainly by insulin resistance. Therefore, how to improve insulin resistance is considered to be one of the most important strategies for treating diabetes. Recently, many reserches have found that the changes in gut microbiota can influence the development of obesity, insulin resistance, and diabetes. Many reports have also indicated that the metabolites derived by gut microbiota may play key role in these functions. In this study, we first chose the palmitic acid -induced insulin resistance in L6 myotubes as the test platform to select effective probiotics metabolites. The results showed that conjugated linoleic acid (CLA), spermidine (SPD) and butyric acid (BTY) were effective metabolites which could increase glucose uptake activity of L6 cells, and the strains that had capacity to produce these selected metabolites were also found. In addition, precursors such as linoleic acid and L-arginine were added to increase the contents of these metabolites. Finally, we used three different probiotics strains to ferment soybean flour to obtain these desired metabolites. We found that the glucose uptake activity of L6 cells treated with the fermented soybean flour extracts was significantly increased to 1.67 times as compared to the control group (the DMSO treated group) and even superior to the results of the positive control group (the insulin treated group). Consequently, the application of the fermented metabolite mixtures might have a potential to improve insulin resistance disorder in the future.