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

Abstract

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.

Vancomycin relieves tacrolimus-induced hyperglycemia by eliminating gut bacterial beta-glucuronidase enzyme activity

“…TAC induced weight loss was common in the diabetic model, and vancomycin did not reverse it here. 42 , 43 No discernible differences in fasting glucose levels were observed among the three groups ( Figure 1b ). A set of tests was performed to assess the effects of TAC on glucose homeostasis and insulin sensitivity.…”

Lack of Improvement in Insulin Sensitivity After Pancreas Transplantation in Recipients With a High Level of Calcineurin Inhibitors

“…Ling et al 18 demonstrated that tacrolimus directly (insulin signaling pathway) and indirectly (hepatic steatosis) leads to hepatic insulin resistance; another study revealed that adipocytokines and Peroxisome Proliferator-Activated Receptor Gamma signaling serve important roles in the pathogenesis of tacrolimus-induced insulin resistance. 19 Considering these effects of calcineurin inhibitors on insulin resistance, it may be reasonable to reduce the dosage of calcineurin inhibitors and to supplement with other immunosuppressants such as mammalian target of rapamycin inhibitors. Also, the changes in MI and HOMA-IR after pancreas transplantation may be affected by the surgical techniques.…”

Exploring the Mechanism of Skeletal Muscle in a Tacrolimus-Induced Posttransplantation Diabetes Mellitus Model on Gene Expression Profiles

“…It has been reported that quadriceps are kinds of oxidative muscle which were closely related to insulin resistance [20] while the muscle fiber types of gastrocnemius are glycolytic type [20]. Our preliminary study had shown peroxisome proliferator-activated receptor-(PPAR-) γ which was related to insulin resistance in Tac-induced PTDM expressed in quadriceps [21]. So, quadriceps and gastrocnemius were dissected from the PTMD model induced by Tac to test this hypothesis.…”