miR-122 dysregulation is associated with type 2 diabetes mellitus-induced dyslipidemia and hyperglycemia independently of its rs17669 variant.

BACKGROUND: miR-122 is a liver specific micro-RNA that participates in the regulation of carbohydrate and lipid metabolism. The rs17669 variant of miR-122 is positioned at the flanking region of miR-122 and may affect its stability and maturation. Therefore, this study was aimed to investigate the association of the rs17669 polymorphism with the miR-122 circulating level, risk of type 2 diabetes mellitus (T2DM) development, and biochemical parameters in T2DM patients and matched healthy controls. METHODS AND RESULTS: This study involved 295 subjects (controls: n = 145 and T2DM: n = 150). The rs17669 variant genotyping was done by ARMS-PCR. Serum biochemical parameters including lipid profile, small-dense low density lipoprotein (sdLDL) and glucose were measured by colorimetric kits. Insulin and Glycated hemoglobin (HbA1c) were assayed using ELISA and capillary electrophoresis methods, respectively. miR-122 expression was measured by real-time PCR. There was no significant difference between study groups in terms of allele and genotype distribution (P > 0.05). The rs17669 variant did not have any significant association with miR-122 gene expression and biochemical parameters (P > 0.05). miR-122 expression level in T2DM patients was significantly higher than that in control subjects (5.7 ± 2.4 vs. 1.4 ± 0.78) (P < 0.001). Furthermore, miR-122 fold change had a positive and significant correlation with low-density lipoprotein cholesterol (LDL-C), sdLDL, fasting blood sugar (FBS), and insulin resistance (P < 0.05). CONCLUSION: It can be concluded that the rs17669 variant of miR-122 is not associated with the miR-122 expression and T2DM-associated serum parameters. Furthermore, it can be suggested that miR-122 dysregulation is involved in T2DM development through inducing dyslipidemia, hyperglycemia, and resistance to insulin.

Green Synthesis and Characterization of Copper Nanoparticles and Their Effects on Liver Function and Hematological Parameters in Mice.

OBJECTIVES: The present investigation is based on the green synthesis of copper nanoparticles (CuNPs) from aqueous extract of Capparis spinosa L. fruit. Their effects on liver function and hematological parameters in mice were evaluated. MATERIALS AND METHODS: The green synthesis of CuNPs by means of C. spinosa extract was achieved. Ultraviolet-visible spectroscopy, fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), and energy dispersive X-ray spectroscopy were used to identify the synthesized nanoparticles. BALB/c mice were orally administrated CuNPs at doses of 1000, 2000, and 5000 µg/kg for 2 weeks. Later, the effects of CuNPs on liver function in the treated mice were evaluated by measuring the serum levels of enzymes such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and bilirubin as well as hematological parameters including hemoglobin, hematocrit, white blood cell, red blood cell, and platelet counts. RESULTS: A maximum peak at wavelength 414 nm confirmed the biosynthesis of CuNPs. FTIR spectrum analysis revealed that the factor groups shaped a coating extract on the surface of the nanoparticles. SEM images demonstrated a particle size between 17 and 41 nm. Although some liver enzymes and hematological parameters increased with increasing dose of extract, there was no significant difference (p>0.05) between oral administrations of CuNPs at doses of 1000, 2000, and 5000 µg/kg and the control group. CONCLUSION: The findings revealed that CuNPs biosynthesized from aqueous extract of C. spinosa fruit have no toxic effects on the liver functions and hematological parameters of mice. However, more studies are needed for evaluation of the hepatoprotective effects of CuNPs.

Resveratrol Attenuates Copper and Zinc Homeostasis and Ameliorates Oxidative Stress in Type 2 Diabetic Rats.

Diabetes is a common metabolic disorder characterized by elevated blood glucose level. Trace element homeostasis causes disturbances in diabetes due to hyperglycemia. Superoxide dismutase (SOD), an antioxidant enzyme, contains zinc and copper ions as its cofactors. Defects in SOD level and activity have been observed in diabetes. Resveratrol (RSV) has displayed hypoglycemic effects and is proven to improve oxidative stress. The aim of the present study was to examine the possible effects of RSV on blood glucose level, serum copper and zinc levels, SOD, and a number of other oxidative markers in type 2 diabetic rats. Diabetes was induced in male Wistar rats with administration of streptozotocin and nicotine amide. The studied groups containing six animals per group were as follows: group 1 normal control group; group 2 diabetic control group; groups 3, 4, and 5 diabetic rats that received 1, 5, and 10 mg/kg body weight of RSV, respectively for 30 days. Serum glucose, copper, zinc, SOD activity, total oxidant status (TOS) as well as thiol groups were all measured. Blood glucose in RSV treated groups significantly decreased. Similarly, copper significantly decreased in diabetic groups treated with RSV. Treatment with 10 mg/kg RSV resulted in significantly increased serum zinc. Furthermore, Cu/Zn ratio was observed to decrease in treated groups compared with untreated diabetic control group. RSV treated groups revealed an increased level of SOD activity as well as improved oxidative status. In summary, the results showed that RSV has potential hypoglycemic effect, attenuates trace element homeostasis, and consequently increases SOD activity level.