著者

松坂 賢 島野 仁

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.142, no.5, pp.473-476, 2022-05-01 (Released:2022-05-01)

参考文献数

9

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The increasing prevalence of obesity worldwide has become an alarming public health concern because of dramatic increases in the incidence of obesity-associated diseases, including type 2 diabetes mellitus (T2DM). Peripheral insulin resistance and impaired insulin secretion remain the core defects in T2DM. Despite significant advances in unraveling the mechanisms underlying these defects, many of the metabolic pathways and regulators involved in insulin resistance and β-cell dysfunction are not completely understood. This review proposes that manipulating the fatty acid (FA) composition by blocking ELOVL fatty acid elongase 6 (Elovl6) could protect against insulin resistance, impaired insulin secretion, and obesity-related disorders. Elovl6 is a microsomal enzyme involved in the elongation of C16 saturated and monounsaturated FAs to form C18 FAs. We have reported that mice with Elovl6 deletion are protected against obesity-induced insulin resistance or β-cell failure because the cellular FA composition is changed, even with concurrent obesity. Therefore, Elovl6 appears to be a crucial metabolic checkpoint, and limiting the expression or activity of Elovl6 could be a new therapeutic approach in the treatment of T2DM.

著者

島野 仁

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.135, no.9, pp.1003-1009, 2015 (Released:2015-09-01)

参考文献数

17

被引用文献数

4

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Recent studies suggest that chronic local inflammation and cellular stresses are the key steps in organ defects in obesity-related diseases such as atherosclerosis, diabetes, and fatty liver. We have shown that an excess energy state activates sterol regulatory element-binding protein (SREBP)-1c, a master transcription factor for fatty acid synthesis causing the accumulation of lipids leading to fatty liver, insulin resistance, insulin secretion defects, and dyslipidemia and we clarified their molecular mechanisms. Recently, we shifted focus to the quality aspect of accumulated lipids. It has long been known that saturated and poly-unsaturated fatty acids are atherogenic and anti-atherogenic, respectively. Besides desaturation, we found that the chain-length of fatty acids is another important factor. Elovl6 that we have cloned as an SREBP-1 target is a fatty acid elongase that catalises the last step of fatty acid synthesis. Elovl6 KO mice exhibit obesity and fatty liver on a high energy diet, but unexpectedly were immune to insulin resistance (Nat. Med., 13, 2007, Matsuzaka et al.), atherosclerosis (Arterioscler. Thromb. Vasc. Biol., 31, 2011, Saito et al.) and non-alcoholic steatohepatitis (NASH) pathology including liver damage, ROS, and fibrosis (Hepatology, 56, 2012, Matsuzaka et al.). Elovl6 is crucial for protection against lung fibrosis (Nat. Commun., 4, 2013, Sunaga et al.). These data implicate that fatty acid composition is a new therapeutic target for a variety of chronic metabolic diseases. In this symposium review, a novel strategy for the prevention of life-related diseases will be discussed in the standpoint of application of wet-dry fusion strategies for theoretical and medicinal chemistry.

著者

古川 祥子 藤原 和哉 尾本 美代子 村山 友樹 呉 龍梅 笹木 晋 熊谷 亮 五十野 桃子 秋根 大 小林 浩幸 高屋敷 典生 鈴木 浩明 島野 仁 野牛 宏晃

出版者

THE JAPAN DIABETES SOCIETY

雑誌

糖尿病 (ISSN:0021437X)

巻号頁・発行日

vol.57, no.12, pp.913-920, 2014

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症例は21歳女性.2年前から繰り返す発熱,倦怠感,頭痛,動悸,嘔気が1ヶ月前より増悪し来院.血圧186/133 mmHg,脈拍106/分,体温38.5 ℃,血液検査上HbA1c 8.2 %,血糖356 mg/d<i>l</i>と糖尿病を認め,CRP 40.21 mg/d<i>l</i>, IL-6 100 pg/m<i>l</i>と高値だった.画像上¹²³I-MIBGシンチグラフィーで集積のある7 cm大の左後腹膜腫瘤を認め,カテコラミン・メタネフリン高値であり褐色細胞腫と診断した.ドキサゾシン,プロプラノロールの他,発熱,炎症反応高値に対しナプロキセンを使用した結果,CRP 0.15 mg/d<i>l</i>, IL-6 1.7 pg/m<i>l</i>まで低下した.同時に耐糖能は改善し,インスリン療法を術前に中止し得た.IL-6高値を伴う褐色細胞腫では,ナプロキセンが二次性糖尿病を改善し,高血糖による手術リスクを減少し得ることが示唆された.

著者

島野 仁

巻号頁・発行日

2012

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科学研究費助成事業(科学研究費補助金)研究成果報告書:基盤研究(B)2009-2011

著者

島野 仁

巻号頁・発行日

2012

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科学研究費助成事業(科学研究費補助金)研究成果報告書:挑戦的萌芽研究2011