Liraglutide combined with human umbilical cord mesenchymal stem cell transplantation inhibits beta‐cell apoptosis via mediating the ASK1/JNK/BAX pathway in rats with type 2 diabetes

Abstract Objective Accumulating evidence suggests an association between beta‐cell apoptosis and the ASK1/JNK/BAX pathway. The aim of this study was to investigate the effects of a combined therapy of liraglutide and human umbilical cord mesenchymal stem cells (hUC‐MSCs) on the glucose metabolism and islet beta‐cell apoptosis, and further explore its relationship to the ASK1/JNK/BAX pathway. Method Type 2 diabetes mellitus (T2DM) rat model was induced by a high‐sugar and high‐fat diet and intraperitoneal injection of low‐dose streptozotocin (STZ) (30 mg/kg). Three days after STZ injection, diabetic rats were randomly treated with subcutaneous injection of liraglutide (200 μg/kg/12 h) for 8 weeks and or hUC‐MSCs (1 × 10 6 /rat) at the first and fifth weeks. Diabetes‐related physical and biochemical parameters, pancreatic histopathological changes, immunohistochemical staining, quantitative real‐time polymerase chain reaction, and western blot were used to measure the expression of apoptosis signal‐regulating kinase 1 (ASK1), Jun N‐terminal kinase (JNK), Bcl‐2 associated X protein (BAX), and B‐cell lymphoma‐2 (Bcl‐2). Results Eight weeks after liraglutide or human umbilical cord mesenchymal stem cell administration, FPG, HbA 1c , glucagon, body weight, and pancreatic ASK1, JNK, and BAX mRNA and proteins were significantly decreased, and the levels of serum C‐p, INS and GLP‐1, ratio of insulin positive area, and Bcl‐2 expression were significantly increased in three treatment groups compared with T2DM group ( P <.05). Conclusion Liraglutide combined with hUC‐MSCs improve glucose metabolism and inhibit islet beta‐cell apoptosis in a ASK1/JNK/BAX pathway‐dependent manner.