近日，美國學術(shù)刊物《細胞—代謝》Cell Metabolism在線刊登了日本研究人員的最新研究成果“PGRN is a Key Adipokine Mediating High Fat Diet-Induced Insulin Resistance and Obesity through IL-6 in Adipose Tissue,，”,，日本研究人員日前在小鼠試驗中發(fā)現(xiàn)了導致胰島素無法有效降糖的蛋白質(zhì)。這種名為顆粒蛋白前體（PGRN）的蛋白質(zhì)很可能是導致肥胖和糖尿病的原因之一,，該發(fā)現(xiàn)有望對診斷和治療糖尿病作出貢獻,。
機體對胰島素的敏感性降低、胰島素難以促進葡萄糖代謝的狀態(tài)被稱為胰島素抵抗,，在主要由暴飲暴食,、缺少運動等不良生活習慣導致的2型糖尿病患者中很常見。
日本神戶大學,、島津制作所等組成的聯(lián)合研究小組成員利用比較分析法,，對小鼠體內(nèi)的蛋白質(zhì)進行了全面研究，結(jié)果發(fā)現(xiàn)與胰島素抵抗有關(guān)的PGRN蛋白質(zhì),，在肥胖小鼠的血液中,，其濃度是正常小鼠的2至3倍。
研究人員將這種蛋白質(zhì)注射到正常小鼠體內(nèi),，結(jié)果后者即使不發(fā)胖,，也會出現(xiàn)胰島素抵抗。此外,，如果阻礙小鼠體內(nèi)生成PGRN蛋白質(zhì),，那么即使喂食高脂食物，小鼠也沒有發(fā)胖,，而且也未發(fā)生胰島素抵抗,。
據(jù)研究者介紹，PGRN蛋白質(zhì)同樣存在于人體,，它有助于炎癥和傷口痊愈,。研究小組成員、神戶大學教授清野進說：“這種蛋白質(zhì)除可以用作確認胰島素抵抗的簡便診斷指標外,，還可能有助于開發(fā)相關(guān)治療藥物,。”（生物谷Bioon.com）
doi:10.1016/j.cmet.2011.12.002
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PGRN is a Key Adipokine Mediating High Fat Diet-Induced Insulin Resistance and Obesity through IL-6 in Adipose Tissue
Toshiya Matsubara, Ayako Mita, Kohtaro Minami, Tetsuya Hosooka, Sohei Kitazawa, Kenichi Takahashi, Yoshikazu Tamori, Norihide Yokoi, Makoto Watanabe, Ei-ichi Matsuo, Osamu Nishimura, Susumu Seino
Adipose tissue secretes adipokines that mediate insulin resistance, a characteristic feature of obesity and type 2 diabetes. By differential proteome analysis of cellular models of insulin resistance, we identified progranulin (PGRN) as an adipokine induced by TNF-α and dexamethasone. PGRN in blood and adipose tissues was markedly increased in obese mouse models and was normalized with treatment of pioglitazone, an insulin-sensitizing agent. Ablation of PGRN (Grn/) prevented mice from high fat diet (HFD)-induced insulin resistance, adipocyte hypertrophy, and obesity. Grn deficiency blocked elevation of IL-6, an inflammatory cytokine, induced by HFD in blood and adipose tissues. Insulin resistance induced by chronic administration of PGRN was suppressed by neutralizing IL-6 in vivo. Thus, PGRN is a key adipokine that mediates HFD-induced insulin resistance and obesity through production of IL-6 in adipose tissue, and may be a promising therapeutic target for obesity.
