Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, Kanagawa, Japan.
Department of Physiology, St. Marianna University School of Medicine, Kanagawa, Japan.
J Diabetes Res. 2020 Jan 13;2020:7614035. doi: 10.1155/2020/7614035. eCollection 2020.
Type 2 diabetes (T2D) is a known risk factor for diabetic kidney disease (DKD) and sarcopenia in older patients. Because there may be an interaction between DKD and sarcopenia, the aim of the present study is to investigate the relationship between urinary levels of liver-type fatty acid-binding protein (L-FABP) and sarcopenia using a novel rat model of T2D.
Male spontaneously diabetic Torii (SDT) fatty rats ( = 5) at 16 weeks of age were used as an animal model of T2D. Age- and sex-matched Sprague-Dawley (SD) rats ( = 7) were used as controls. Urine samples were obtained from the rats, and muscle strength was evaluated with the use of the forelimb grip test at 16, 20, and 24 weeks of age. Serum, kidney, soleus, and extensor digitorum longus (EDL) muscle samples were collected at 24 weeks of age. Urinary L-FABP levels were measured using dedicated enzyme-linked immunosorbent assays.
Increased urinary L-FABP levels, focal glomerular sclerosis, moderate interstitial inflammation and fibrosis, and accumulation of renal oxidative proteins were significantly observed in the SDT fatty rats, compared to the SD rats. Muscle weight, muscle strength, cross-sectional areas of both type I and type IIb muscle fibers, and increasing rate of muscle strength were significantly decreased in the SDT fatty rats compared to the SD rats at 24 weeks. Urinary L-FABP levels at 20 and 24 weeks were significantly negatively correlated with muscle strength. Urinary L-FABP levels at 16 weeks were significantly negatively correlated with the increasing rate of muscle strength.
Urinary L-FABP reflects the degree of muscle strength and weight, as well as cross-sectional areas of muscle fibers. Although further clinical study is needed, urinary L-FABP may be useful to monitor the progression of sarcopenia and DKD in T2D patients.
2 型糖尿病(T2D)是老年患者糖尿病肾病(DKD)和肌肉减少症的已知危险因素。由于 DKD 和肌肉减少症之间可能存在相互作用,本研究旨在使用新型 T2D 大鼠模型研究肝型脂肪酸结合蛋白(L-FABP)尿液水平与肌肉减少症之间的关系。
16 周龄雄性自发性糖尿病 Torii(SDT)肥胖大鼠(n=5)被用作 T2D 动物模型。年龄和性别匹配的 Sprague-Dawley(SD)大鼠(n=7)作为对照。在 16、20 和 24 周龄时,从大鼠中获取尿液样本,并使用前肢握力测试评估肌肉力量。在 24 周龄时收集血清、肾脏、比目鱼肌和伸趾长肌(EDL)肌肉样本。使用专用酶联免疫吸附测定法测量尿 L-FABP 水平。
与 SD 大鼠相比,SDT 肥胖大鼠的尿 L-FABP 水平升高,局灶性肾小球硬化,中度间质炎症和纤维化,以及肾氧化蛋白积累明显。与 SD 大鼠相比,SDT 肥胖大鼠的肌肉重量、肌肉力量、I 型和 IIb 型肌纤维的横截面积以及肌肉力量的增加率在 24 周时明显降低。20 和 24 周时的尿 L-FABP 水平与肌肉力量呈显著负相关。16 周时的尿 L-FABP 水平与肌肉力量的增加率呈显著负相关。
尿 L-FABP 反映了肌肉力量和重量以及肌纤维的横截面积。尽管需要进一步的临床研究,但尿 L-FABP 可能有助于监测 T2D 患者肌肉减少症和 DKD 的进展。