Altered expression of glucose metabolism associated genes in a tacrolimus‑induced post‑transplantation diabetes mellitus in rat model

• Published in: International journal of molecular medicine Vol. 44; no. 4; pp. 1495 - 1504
• Main Authors: Zhang, Ling, He, Yunqiang, Wu, Cunzao, Wu, Minmin, Chen, Xuehai, Luo, Jiao, Cai, Yong, Xia, Peng, Chen, Bicheng
• Format: Journal Article
• Language: English
• Published: Greece Spandidos Publications 01-10-2019; Spandidos Publications UK Ltd
• Subjects: Animals; Biomarkers; Carbohydrate Metabolism - genetics; Diabetes mellitus; Diabetes Mellitus, Experimental - etiology; Diabetes Mellitus, Experimental - metabolism; Disease Models, Animal; Gene Expression; Gene Expression Regulation; Genes; Glucose; Glucose - metabolism; Glucose Intolerance; Hyperglycemia; Immunosuppressive agents; Immunosuppressive Agents - adverse effects; Insulin; Insulin - metabolism; Insulin resistance; Liver; Male; Organ Specificity; Organ transplant recipients; Organ Transplantation - adverse effects; Proteins; Rats; Rodents; Signal Transduction; Studies; Surgery; Tacrolimus; Tacrolimus - adverse effects; Thiazolidinediones; China
• ISSN: 1107-3756; 1791-244X
• DOI: 10.3892/ijmm.2019.4313

Post‑transplantation diabetes mellitus (PTDM) is a known side effect in transplant recipients administered with immunosuppressant drugs, such as tacrolimus (Tac). Although injury of islet cells is considered a major reason for Tac‑induced PTDM, the involvement of insulin resistance in PTDM remains unknown. In the present study, expression levels of adipocytokines, glucose metabolism associated genes and peroxisome proliferator‑activated receptor (PPAR)‑γ in adipose, muscular and liver tissues from a rat model induced with Tac (1 mg/kg/day) were examined. Rats developed hyperglycemia and glucose intolerance after 10 days of Tac administration. A subgroup of diabetic rats was further treated with rosiglitazone (4 mg/kg), a PPAR‑γ activator. Adipose, muscle and liver tissues were obtained on day 15 after induction and the results demonstrated that expression levels of adipocytokines, PPAR‑γ and proteins in the insulin associated signaling pathway varied in the different groups. Rosiglitazone administration significantly improved hyperglycemia, glucose intolerance and expression levels of proteins associated with insulin signaling, as well as adipocytokines expression. The results of this study demonstrated that adipocytokines and PPAR‑γ signaling may serve important roles in the pathogenesis of Tac‑induced PTDM, which may provide a promising application in the treatment of PTDM in the future.