近日，美国学术刊物《细胞—代谢》Cell Metabolism在线刊登了日本研究人员的最新研究成果“PGRN is a Key Adipokine Mediating High Fat Diet-Induced Insulin Resistance and Obesity through IL-6 in Adipose Tissue，”，日本研究人员日前在小鼠试验中发现了导致胰岛素无法有效降糖的蛋白质。这种名为颗粒蛋白前体（PGRN）的蛋白质很可能是导致肥胖和糖尿病的原因之一，该发现有望对诊断和治疗糖尿病作出贡献。
机体对胰岛素的敏感性降低、胰岛素难以促进葡萄糖代谢的状态被称为胰岛素抵抗，在主要由暴饮暴食、缺少运动等不良生活习惯导致的2型糖尿病患者中很常见。
日本神户大学、岛津制作所等组成的联合研究小组成员利用比较分析法，对小鼠体内的蛋白质进行了全面研究，结果发现与胰岛素抵抗有关的PGRN蛋白质，在肥胖小鼠的血液中，其浓度是正常小鼠的2至3倍。
研究人员将这种蛋白质注射到正常小鼠体内，结果后者即使不发胖，也会出现胰岛素抵抗。此外，如果阻碍小鼠体内生成PGRN蛋白质，那么即使喂食高脂食物，小鼠也没有发胖，而且也未发生胰岛素抵抗。
据研究者介绍，PGRN蛋白质同样存在于人体，它有助于炎症和伤口痊愈。研究小组成员、神户大学教授清野进说：“这种蛋白质除可以用作确认胰岛素抵抗的简便诊断指标外，还可能有助于开发相关治疗药物。”（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.
