Renal Pathophysiology Laboratory, Investigation On Diabetes Complications, State University of Campinas (UNICAMP), Rua Tessália Vieira de Camargo, 126 - Cidade Universitária, Campinas, SP, 13083-887, Brasil.
Laboratory of Exercise Physiology, School of Physical Education, State University of Campinas (UNICAMP), Campinas, SP, Brazil.
Sci Rep. 2022 May 31;12(1):9062. doi: 10.1038/s41598-022-13054-y.
In patients with diabetes, it has been suggested that physical exercise may reduce albuminuria and the progression of renal disease. However, the molecular mechanism by which physical exercise protects the kidney in diabetes remains poorly understood. The aim of the present study was to determine the contribution of muscle irisin secretion induced by aerobic physical exercise with the subsequent activation of AMPK for kidney protection under diabetic conditions. Aerobic physical exercise in rats protected the kidney in streptozotocin-induced diabetes. It reduced albuminuria, glomerular hypertrophy, and glomerular expression of collagen IV and fibronectin, as well as markers of kidney inflammation, when compared to sedentary diabetic rats. These effects were associated with elevation in muscle FNDC5/irisin and activity of AMPK in the diabetic kidney. However, the beneficial effects of exercise were lost when the diabetic rats were treated with CycloRGDyK, that in the bone it has been described as an irisin receptor blocker. In cultured human tubular (HK-2) cells, treatment with recombinant irisin counteracted the effect of high glucose in a dose-dependent manner. Irisin, per se, also activated AMPK in HK-2 cells. It is concluded that in diabetes, the renal protective effect of exercise may be mediated by the irisin/AMPK pathway.
在糖尿病患者中，运动被认为可以减少蛋白尿和肾脏疾病的进展。然而，运动如何保护糖尿病患者的肾脏的分子机制仍知之甚少。本研究旨在确定有氧运动诱导的肌肉鸢尾素分泌及其随后激活 AMPK 对糖尿病状态下肾脏保护的作用。在链脲佐菌素诱导的糖尿病大鼠中，有氧运动可保护肾脏。与久坐的糖尿病大鼠相比，有氧运动降低了白蛋白尿、肾小球肥大以及肾小球Ⅳ型胶原和纤维连接蛋白的表达，以及肾脏炎症标志物的表达。这些作用与肌肉 FNDC5/鸢尾素的升高和糖尿病肾脏中 AMPK 的活性有关。然而，当糖尿病大鼠用 CycloRGDyK 治疗时，运动的有益作用就消失了，CycloRGDyK 在骨骼中被描述为一种鸢尾素受体阻断剂。在培养的人肾小管（HK-2）细胞中，重组鸢尾素以剂量依赖性方式拮抗高葡萄糖的作用。鸢尾素本身也能激活 HK-2 细胞中的 AMPK。综上所述，在糖尿病中，运动的肾脏保护作用可能是通过鸢尾素/AMPK 途径介导的。
