陰電性低密度脂蛋白對於 RIN-m5F beta 細胞分泌胰島素的影響

The Effects of Electronegative LDL on Insulin Secretion of RIN-m5F Beta Cells

林忻婷(Hsin-Ting Lin)

指導教授 ： 吳世忠

高雄醫學大學/健康科學院/生物醫學檢驗學研究所/碩士(2014年)

摘要

研究指出高血脂症(hyperlipidemia)與糖尿病(diabetes)的形成有關，並認為高血脂症中的低密度脂蛋白(LDL)與胰臟的β 細胞衰竭有著密切的關係，然而 LDL 是否會造成β 細胞的傷害，仍存在著不同爭議性。近來我們團隊將 LDL 以陰電性強弱作為分類，證實陰電性最強的低密度脂蛋白 (L5) 會對內皮細胞造成細胞毒性，也發現到糖尿病病人體內比正常人含有較高的 L5，但 L5與糖尿病形成是否有關或其對β 細胞是否造成影響仍需進一步驗證，因此本研究利用 RIN-m5F β細胞株來觀察 L5對β 細胞分泌胰島素的影響。

我們發現同樣在50 μg/mL 的濃度，L5刺激後會抑制胰臟β細胞分泌胰島素(insulin)，並且 L5 也會造成β細胞對於高糖刺激下分泌 insulin 的反應減弱。同時也發現到 L5具有刺激β細胞內氧化壓力增加的趨勢，並引起 JNK pathway 的磷酸化，另外L5也會抑制 insulin 基因表現。然而相對於 L5，L1(LDL中陰電性最弱)並不會造成β細胞的傷害與功能受損。由我們的研究結果推測，人體內 L5的含量增加會導致β細胞衰竭，因此在糖尿病的病情發展過程中，可能會由於 L5的增加進而導致胰臟β細胞逐漸衰竭，而成為糖尿病後期 insulin 分泌量減少的原因。

關鍵字

陰電性脂蛋白 ； 第二型糖尿病 ； 高血脂症

並列摘要

Hyperlipidemia has been indicated as an important factor of contributing to the progression of diabetes. The increase of LDL in hyperlipidemia has also been proposed to be associated with the failure of pancreatic beta cell. However, whether native LDL or modified LDL causes dysfunctional effect of insulin secretion in β cells is still elusive. Because there are different electricity of LDLs found in the plasma, our team demonstrated the strongest electronegative low-density lipoprotein (L5) which can cause the endothelial cell cytotoxicity. Also they found that diabetic patients contain the higher level of L5 than healthy people. This study aims to identify the mechanisms of electronegtive LDL (L5) and L1 (less electronegtive LDL) acting on the insulin secretion of pancreatic β-cells.

RIN-m5F cells, a rat pancreatic cell line, were cultured with human native L1 or L5. Our results showed that at 50 ug/mL, L5 inhibited the insulin secretion of pancreatic β cell. We also found that L5 reduced the response of insulin release stimulated by high glucose. Oxidative stress and JNK pathway phosphorylation were activated after treating RIN-m5F cells with L5, but insulin gene was suppressed by L5. Compared with L5, L1 didn’t cause RIN-m5F cells damage and dysfunction. According to our results, we suggest the increasing of L5 in our body may cause β cell failure. Therefore, in the processes of diabetes developing, the increasing of L5 may cause the pancreatic β cell failure, which is the reason of decreasing of insulin secretion in the post-dibetes.

並列關鍵字

Electronegative LDL ； T2D ； hyperlipidemia

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