Apelin‑13 alleviates diabetic nephropathy by enhancing nitric oxide production and suppressing kidney tissue fibrosis

Abstract

Diabetes is a serious metabolic disease, and the kidney damage induced by diabetes also seriously affects the survival of patients. Apelin is a molecule that plays a crucial role in lipid metabolism, and recent studies have revealed that apelin-13, a subtype of apelin, plays an important role in regulating blood glucose levels. However, the role of apelin-13 in diabetic nephropathy remains unclear. In the present study, a rat model of diabetic nephropathy was constructed by the injection of streptozocin (STZ). During this process, these rats were injected with apelin-13. The blood glucose, urine protein and insulin levels were determined weekly. Next, the expression of angiotensin domain type 1 receptor-associated protein (APJ), endothelial nitric oxide synthase (eNOS), E-cadherin and α-smooth muscle actin (α-SMA) in the kidney tissues was determined with western blotting. Then, the endothelial cells of glomerular vessels were cultured with high glucose medium. These cells were treated with apelin-13 for 24 h. Finally, cell viability of these cells and the expression of APJ, eNOS, E-cadherin and α-SMA in these cells were determined with western blotting. As a result, treatment of apelin-13 induced the lower levels of blood glucose and urine protein.In addition, application of apelin-13 promoted the production of insulin and alleviated the insulin resistance. Treatment with apelin-13 promoted the expression of APJ, eNOS and E-cadherin while it suppressed the expression of α-SMA in kidney tissues of rats and endothelial cells of glomerular vessels. Furthermore, application of apelin-13 also promoted the cell viability of these cells. In conclusion, apelin-13 relieved diabetic nephropathy by promoting the production of nitric oxide (NO) and alleviating the fibrosis of kidney tissues.

Expression of apelin‑13 and its negative correlation with TGF‑β1 in patients with diabetic kidney disease

“…Apelin-13 may be positively correlated with urinary protein and promote the progress of DKD by increasing fat mass, promoting angiogenesis in glomeruli to form abnormal vessels, increasing permeability or inducing podocyte apoptosis (18). However, it has also been reported that apelin inhibited the process of EMT in podocytes in diabetic KK-Ay mice (34), decreased the levels of TGF-β and suppressed kidney tissue fibrosis in Sprague Dawley rats with diabetic nephropathy (35). Therefore, apelin-13 may be relevant to increased fat mass, increased glomerular permeability and induced podocyte apoptosis during the early stages of DKD, while it may inhibit renal fibrosis in the advanced stage of DKD.…”

The role of polyunsaturated fatty acids: The possibility of diet intervention in Parkinson's disease

“…[50], are regulated by apelin. Some apelin subtypes cause the generation of NO, which leads to vasodilatation [51]. What's more, APJ is abundantly distributed throughout the central nervous system [52], although it is yet unknown how APJ interacts with ω-3.…”

The Role of Apelin–APJ System in Diabetes and Obesity

“…It provides negative feedback for insulin secretion ( 41 ). On the contrary, Gao Z et al reported that the administration of apelin-13 significantly reduces blood glucose and increases serum insulin level ( 43 ). Besides these, long-term apelin administration significantly improves pancreatic islet mass and insulin level in diabetes ( 44 ).…”