ABSTRACT
Type 2 diabetes (T2DM) is associated with an increased vascular disease. Moreover, endothelial progenitor cell (EPC) function is impaired in diabetic patients. Decreased EPC number plays a critical role in reduced endothelial repair and development of the vascular disorder. To determine the effect of metformin and insulin plus metformin on functional activity of EPCs, 130 participants were divided into three groups (group 1: healthy control; group 2: metformin; group 3: insulin plus metformin). The concentration of EPCs in the circulation was first quantified. Thereafter, circulating EPCs (cEPCs) were harvested and the biological features of these cells including proliferative, clonogenicity, tubulogenic, and migratory properties were analyzed after expansion. The serum protein levels of some proangiogenic factors were also measured. Our results showed greater numbers of cEPCs in control and in diabetic patients treated with insulin plus metformin than in metformin-treated patients. Insulin plus metformin therapy was associated with augmented proliferative, clonogenicity, migratory, and tubulogenic activity of cEPCs in patients with T2DM. Increased serum concentrations of angiogenic factors were also observed in patients treated with insulin plus metformin. Western blot analysis showed increased protein levels of pTie-2/Tie2 and Pakt/AKT in cEPCs harvested from T2DM, treated with insulin metformin plus. This study showed that treatment with insulin plus metformin in diabetic patients is associated with increased mobilization of EPCs into the circulation, with potential beneficial effect in vascular protection in diabetic patients.
ABSTRACT
BACKGROUND: Autism spectrum disorder (ASD) is a pediatric heterogeneous psychiatric and neurodevelopmental disorder with social and communication deficits, language impairment and ritualistic or repetitive behaviors. ASD has significant genetic bases but candidate genes and molecular mechanisms of disorder are not clarified. Neuregulin1 (NRG1) gene, located in 8p12 is involved in development of central nervous system and was indicated as candidate gene in schizophrenia. METHODS: mRNA level of types I, II and III of NRG1 gene were studied in peripheral blood of 1540 ASD patients (IQâ¯>â¯70) and 1490 control children by quantitative Real Time PCR. Also three domains of executive functions (working memory, response inhibition and vigilance) were examined in all subjects. FINDINGS: All three types were significantly down regulated in ASD patients. Significant deficiencies in executive functions (EF) were found in ASD patients. EF deficiencies mostly were associated with down expression of mRNA level of types I and III. Also correlations were found between NRG1 expression with gender and severity of ASD symptoms. INTERPRETATIONS: Findings primarily have been suggested involvement of NRG1 in etiology of ASD. Also correlation of NRG1 mRNA level with EF deficiencies could shed lights on EF mechanisms and may suggest targeted treatments to improve particular executive functions. FUND: Young researchers and elites club funded the project due to the annual grant of special talents of Club that gave to Arvin Haghighatfard.
