（封面圖片：背景圖片顯示了高脂肪飲食小鼠的胰腺組織的電子顯微鏡圖像,，其中表現(xiàn)出一個(gè)自噬體螯合線粒體和胰島素顆粒的過程。下面右側(cè)的免疫組織化學(xué)圖像顯示了缺少自噬相關(guān)基因atg7的胰島β細(xì)胞存在損傷標(biāo)志物p62（綠色部分）的聚集,。其中紅色部分為胰島素,，藍(lán)色部分為細(xì)胞核。左側(cè)圖像顯示出atg7-/-胰島當(dāng)中p62內(nèi)含體的發(fā)展過程,。圖像提供：Ebato等）
自噬作用（autophagy）是一種普遍存在于真核細(xì)胞中的現(xiàn)象,，它是溶酶體對(duì)于自身結(jié)構(gòu)的吞噬降解，是細(xì)胞內(nèi)的再循環(huán)系統(tǒng),。細(xì)胞通過自噬作用降解蛋白質(zhì)和受損的細(xì)胞器,。盡管錯(cuò)調(diào)的自噬作用與多種疾病有關(guān)，其中包括神經(jīng)退化性疾病,，但是它在胰腺β細(xì)胞和葡萄糖代謝過程中的作用并未得到很好的揭示,。在2008年10月8日出版的《細(xì)胞—代謝》（Cell Metabolism）上，兩個(gè)國(guó)際研究小組分別發(fā)表了他們?cè)谶@一方面的最新研究成果,。
來(lái)自韓國(guó)和日本的一組科學(xué)家利用了一種特異性去除Atg7（自噬相關(guān)7）基因胰腺β細(xì)胞的小鼠,，Atg7變異的小鼠表現(xiàn)出葡萄糖耐量減低（impaired glucose tolerance）以及血清胰島素濃度的降低。由于細(xì)胞凋亡的增加以及β細(xì)胞分裂增生程度的降低,，導(dǎo)致β細(xì)胞數(shù)量和胰腺中胰島素的減少,。
生理學(xué)分析顯示，在小鼠中存在血糖激發(fā)的胰島素分泌的降低,，并且自噬作用缺陷的β細(xì)胞中血糖誘導(dǎo)的胞內(nèi)鈣離子瞬變過程也被破壞,。而形態(tài)學(xué)分析則表明存在泛素蛋白（ubiquitinated protein）的聚集,，這種現(xiàn)象與p62共存，并伴隨著線粒體腫脹,、內(nèi)質(zhì)網(wǎng)膨脹以及β細(xì)胞液泡的變化,。以上研究結(jié)果表明自噬作用對(duì)于維持胰腺β細(xì)胞的結(jié)構(gòu)、數(shù)量以及功能都是非常重要的,，自噬作用的破壞將導(dǎo)致胰島素的缺乏以及高血糖癥的發(fā)生,。
在另一篇文章中，來(lái)自日本的一組科學(xué)家稱他們發(fā)現(xiàn)了糖尿病db/db小鼠以及高脂飲食C57BL/6小鼠的胰腺β細(xì)胞中存在自噬作用的升調(diào)節(jié),。而能導(dǎo)致糖尿病相關(guān)的外周胰島素抵抗的游離脂肪酸（free fatty acid FFA）誘導(dǎo)胰腺β細(xì)胞自噬作用發(fā)生,。對(duì)于atg7基因的消除將導(dǎo)致胰島退化、胰島素分泌以及葡萄糖耐量降低,。
與此同時(shí)研究人員還觀察到,，盡管在對(duì)照組小鼠中高脂肪含量的飲食能激發(fā)胰腺β細(xì)胞自噬，但是對(duì)于自噬不足變異小鼠而言,，這將形成葡萄糖耐量的惡化,，以上現(xiàn)象發(fā)生的部分原因在于缺乏胰腺β細(xì)胞數(shù)量的補(bǔ)償性增加。
因此,，基礎(chǔ)自噬作用對(duì)于維持正常的胰島結(jié)構(gòu)和功能至關(guān)重要,。文章中作者還表示，當(dāng)存在高脂肪飲食誘導(dǎo)的胰島素抵抗時(shí),，自噬作用是一種胰腺β細(xì)胞的獨(dú)特適應(yīng)性反應(yīng),。（生物谷Bioon.com）
生物谷推薦原始出處：
Cell Metabolism，Vol 8, 318-324, 08 October 2008,，Hye Seung Jung, Myung-Shik Lee
Loss of Autophagy Diminishes Pancreatic β Cell Mass and Function with Resultant Hyperglycemia
Hye Seung Jung,1 Kun Wook Chung,1 Jeong Won Kim,1 Jin Kim,2 Masaaki Komatsu,3,4,5Keiji Tanaka,3 Yen Hoang Nguyen,6 Tong Mook Kang,6 Kun-Ho Yoon,7 Ji-Won Kim,7 Yeon Taek Jeong,1 Myoung Sook Han,1 Moon-Kyu Lee,1 Kwang-Won Kim,1 Jaekyoon Shin,8 and Myung-Shik Lee1
1 Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong Kangnam-ku, Seoul 135-710, Korea
2 Department of Anatomy and Cell Death Disease Research Center, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-ku, Seoul 137-701, Korea
3 Laboratory of Frontier Science, Tokyo Metropolitan Institute of Medical Science, Bunkyo-ku, Tokyo 113-8613, Japan
4 Department of Biochemistry, Juntendo University School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan
5 PRESTO, Japan Science and Technology Corporation, Kawaguchi 332-0012, Japan
6 Department of Physiology, Sungkyunkwan University School of Medicine, Suwon 440-746, Korea
7 Department of Endocrinology and Metabolism, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-ku, Seoul 137-701, Korea
8 Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 440-746, Korea
Autophagy is a cellular degradation-recycling system for aggregated proteins and damaged organelles. Although dysregulated autophagy is implicated in various diseases including neurodegeneration, its role in pancreatic β cells and glucose homeostasis has not been described. We produced mice with β cell-specific deletion of Atg7(autophagy-related 7). Atg7 mutant mice showed impaired glucose tolerance and decreased serum insulin level. β cell mass and pancreatic insulin content were reduced because of increased apoptosis and decreased proliferation of β cells. Physiological studies showed reduced basal and glucose-stimulated insulin secretion and impaired glucose-induced cytosolic Ca2+ transients in autophagy-deficient β cells. Morphologic analysis revealed accumulation of ubiquitinated protein aggregates colocalized with p62, which was accompanied by mitochondrial swelling, endoplasmic reticulum distension, and vacuolar changes in β cells. These results suggest that autophagy is necessary to maintain structure, mass and function of pancreatic β cells, and its impairment causes insulin deficiency and hyperglycemia because of abnormal turnover and function of cellular organelles.
