Kang Young Sun, Lee Mi Hwa, Song Hye Kyoung, Kim Jung Eun, Ghee Jung Yeon, Cha Jin Joo, Lee Ji Eun, Kim Hyun Wook, Han Jee Young, Cha Dae Ryong
Department of Nephrology , Korea University Medical College, Ansan, South Korea.
Kidney Blood Press Res. 2016;41(3):311-24. doi: 10.1159/000443433. Epub 2016 May 25.
BACKGROUND/AIMS: Visfatin is a known adipokine which may improve insulin resistance in obesity and have an anti-diabetic effect via the insulin receptor. We studied the effects of visfatin on diabetic nephropathy in type 2 diabetic mice.
Diabetic male db/db mice were treated with intraperitoneal injections of visfatin. Basal parameters were measured in all mice and glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed in diabetic mice. The histopathological and molecular changes were evaluated in diabetic nephropathy.
Visfatin treatment had no effect on body weight, water and food intake, urinary volume, blood glucose, and HbA1c level. However, visfatin improved HOMA-IR, GTT, ITT and decreased plasma insulin and visfatin level, but not adiponectin level. Plasma cholesterol and triglyceride level were also improved by visfatin treatment. Significantly, visfatin decreased albuminuria in diabetic mice. Glomerulosclerotic change and mesangial expansion in the kidneys were significantly reduced. In addition, visfatin inhibited the expression of proinflammatory and profibrotic cytokines such as MCP-1, TGFβ1, type IV collagen, and PAI-1. The enzymes related to lipid metabolism in the kidney, HMG-CoAR was suppressed by visfatin treatment, whereas FXR and ABCA1 were significantly elevated by treatment.
Visfatin might have a protective effect in diabetic nephropathy without the hypoglycemic effect.
背景/目的：内脂素是一种已知的脂肪因子，可能改善肥胖症中的胰岛素抵抗，并通过胰岛素受体发挥抗糖尿病作用。我们研究了内脂素对2型糖尿病小鼠糖尿病肾病的影响。
对糖尿病雄性db/db小鼠进行腹腔注射内脂素治疗。测量所有小鼠的基础参数，并对糖尿病小鼠进行葡萄糖耐量试验（GTT）和胰岛素耐量试验（ITT）。评估糖尿病肾病的组织病理学和分子变化。
内脂素治疗对体重、水和食物摄入量、尿量、血糖和糖化血红蛋白水平无影响。然而，内脂素改善了稳态模型评估的胰岛素抵抗（HOMA-IR）、GTT、ITT，并降低了血浆胰岛素和内脂素水平，但对脂联素水平无影响。内脂素治疗还改善了血浆胆固醇和甘油三酯水平。值得注意的是，内脂素降低了糖尿病小鼠的蛋白尿。肾脏中的肾小球硬化改变和系膜扩张明显减轻。此外，内脂素抑制促炎和促纤维化细胞因子如单核细胞趋化蛋白-1（MCP-1）、转化生长因子β1（TGFβ1）、IV型胶原和纤溶酶原激活物抑制剂-1（PAI-1）的表达。内脂素治疗抑制了肾脏中与脂质代谢相关的酶3-羟基-3-甲基戊二酰辅酶A还原酶（HMG-CoAR），而法尼醇X受体（FXR）和ATP结合盒转运体A1（ABCA1）在治疗后显著升高。
内脂素可能对糖尿病肾病具有保护作用，而无降血糖作用。
