ABSTRACT
BACKGROUND: New-onset diabetes after transplantation (NODAT) is a serious complication which runs the risk of infections, morbidity and mortality. OBJECTIVE: To evaluate M235T and T174M polymorphisms of angiotensinogen gene along with some demographic and clinical factors including age; sex; body mass index (BMI); model for end-stage liver disease (MELD) score; prednisolone, mycophenolate mofetil and tacrolimus dose; and serum level in NODAT among liver recipients. METHODS: In this study 115 patients (53 with and 62 without NODAT) who had no history of diabetes before the transplantation were investigated. Furthermore, 80 randomly selected apparently healthy people (no transplantation) were used as the control group. Two angiotensinogen polymorphisms (M235T and T174M) were studied using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). RESULTS: Patients included 68 (59.1%) females and 47 (40.9%) males; they had a mean±SD age of 37.4±16.9 years. The M allele frequency was 55.7% (n=128) in M235T and 20.0% (n=46) in T174M polymorphisms. Binary logistic regression analysis confirmed that age (p=0.005), prednisolone dose (p<0.001) and mutated M235T polymorphism (p=0.003) were independent risk factors. CONCLUSION: Presence of M235T T allele may significantly (p<0.001) increase the NODAT risk, and increase the likelihood of developing end-stage liver disease (p=0.003). T174M T allele had a significantly (p=0.007) higher frequency in NODAT group.
ABSTRACT
Recent studies have proposed cell therapy as an alternative therapeutic strategy for many disease states such as diabetes mellitus. Among different cell types mesenchymal stem cells (MSC) have attracted a significant attention based on their intriguing potentials. However MSC therapy is limited as a large portion of transplanted cells undergo apoptosis after transplantation. Therefore, proposing a strategy to overcome this obstacle may be of great value. Recent studies have shown that hypoxia preconditioning (HPC) may improve cell viability after transplantation. Both HPC and hyperglycemia are reported to exert effects by different levels of ROS overproduction. Overdose of ROS in this case would trigger the apoptosis and thereby decreased cell viability after transplantation. Apelin; the endogenous ligand for the previously orphaned G protein-coupled receptor APJ is shown to exert anti apoptotic effects On oxidative stress-induced apoptosis in MSCs via MAPK/ERK1/2 and PI3K/AKT signaling pathways. Accordingly it has been hypothesized that pretreatment of HPC-MSC(s) with apelin 13 would be an effective approach to modify and possibly enhance the efficacy of MSCs in cell therapy of diabetes.
