Aims/hypothesis Obesity is associated with insulin resistance and inflammation. The circulating human mononuclear cell (MNC) has been shown to respond to low-dose insulin infusion. We have now investigated whether in obesity: (1) phosphorylated insulin receptor beta subunit (p-INSR-β) is reduced in the MNC; (2) pro-inflammatory mediators including inhibitor of kappa light polypeptide gene enhancer in B cells-kinase beta (IKBKB), suppressor of cytokine signalling-3 (SOCS) and protein kinase C-beta 2 (PRKCB2) are increased and related to p-INSR-β; and (3) the reduction in MNC p-INSR-β is related to the reduction in insulin sensitivity. Materials and methods MNCs were prepared from fasting blood samples of 16 normal weight and 16 obese female subjects. Results Our data show that p-INSR-β is reduced significantly in MNCs from obese subjects compared with that of normal controls. MNCs from obese subjects have higher IKBKB expression, increased nuclear factor kappa B (NFκB) binding and higher mRNA expression of TNFAIP1 and IL6 genes. NFκB binding, TNFAIP1 mRNA and plasma C-reactive protein are inversely related to p-INSR-β. PRKCB2 mRNA and protein expression were significantly higher in the obese subjects and were related significantly to pro-inflammatory mediators but not to p-INSR-β. SOCS3 mRNA expression was markedly elevated and positively related to proinflammatory mediators including IKBKB and PRKCB2 on the one hand and inversely related to p-INSR-β on the other. Conclusions/interpretation We conclude that in obesity the MNC is characterised by reduced p-INSR-β and increased inflammatory mediators including IKBKB, PRKCB2 and SOCS3. The increase in SOCS3 but not IKBKB or PRKCB2 is related inversely to p-INSR-β and might mediate the inhibition of p-INSR-β. These data elucidate the relationship between inflammation and insulin resistance using the MNC as a model.

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Zinc oxide nanoparticles (ZnO NPs) demonstrate potential positive effects on reproduction. However, their protective role against the reproductive toxicity pollutants has not yet been adequately studied at the molecular level. This study was designed to assess this objective using Benzo[α]pyrene B[a]P as reproductive toxic agent . Forty-eight mature male rats were randomly distributed into six groups: Group1 (negative control); Groups 2 and 3 (positive control I and II, wherein the animals were treated with 10 and 30 mg ZnO NPs/kg BW, respectively); Group 4 (B[a]P group; treated with 150 mg B[a]P/kg BW); and Groups 5 and 6 (subjected to B[a]P treatment co-administered with different concentrations of ZnO NPs). We investigated oxidative stress biomarkers; cholesterol side-chain cleavage enzyme (CYP11A1), steroidogenic acute regulatory protein (StAR), and 3β-hydroxysteroid dehydrogenase (3β-HSD) gene expression; testosterone levels; and histopathology of the liver, kidney, and testicles. The B[a]P-treated group showed significant deterioration in all reproductive parameters and displayed induced oxidative stress. ZnO NPs remarkably reduced oxidative stress, effectively upregulated the mRNA levels of CY11A1, StAR, and 3β-HSD, and improved the histological pictures in the examined organs. At their investigated doses and given their NPs properties, ZnO NPs demonstrated a marked ameliorative effect against the reproductive toxic effects of B[a]P. Further studies are needed to thoroughly investigate the molecular mechanisms of ZnO NPs.

Although Zinc oxide nanoparticles (ZnO NPs) in low doses have potentially positive effects on reproduction by their antioxidant effects, the defensive role of Zinc nanomaterials against environmental pollutants that affect male reproduction has not been adequately studied. We designed our study to assess the impact of ZnO NPs towards reproductive dysfunction induced by Benzo[α]Pyrene (B[a]P). Forty-eight mature male rats were randomly distributed into six equal groups: G1; negative control, G2&3- positive control I &II (either 10 or 30 mg ZnO NPs / kg BW); G4. (150 mg Bap / kg BW), G 5 & 6 (Co- administrated B[a]P with different concentrations of ZnO NPs). Oxidative stress biomarkers, semiquantitative real-time PCR for steroidogenic enzymes (CY11A1, StAR, and 3β- HSD), testosterone levels and histopathology in the liver, kidney, and testicles were examined for this investigation. B[a] P treated group showed significant deterioration in all reproductive parameters and induced oxidative stress. Co-administration ZnO NPs eased oxidative stress and effectively increased the expression of CY11A1, StAR, and 3β- HSD and improved histopathological changes in the examined organs. Our results using the selected doses and with Nano particle properties confirm that ZnO NPs have an obvious ameliorative effect against B[a] P.

Introduction: Hypertension and diabetes mellitus are chronic medical conditions that frequently coexist. Our objective is to evaluate the effect of Angiotensin converting enzyme inhibitors and Angiotensin II receptor blockers comparatively and in integration with Metformin, dipeptidyl 4 inhibitors and insulin on lipid profile, serum creatinine, liver enzymes and electrolytes in type II diabetic patients.Methodology: Data of the study were collected from clinical reports of 100 hypertensive patients with type II diabetes from Taif Diabetic Center. Male and non-pregnant female with an average age (55 ± 10 years) who's treated with ACE Inhibitors and ARBs were our target.Results: Our results recorded that, ARBs significantly increase AST in compared to ACE inhibitors while chloride level decrease with ACE inhibitors in compared to ARBs.On other hand, when we compared the effect of ACE/ARBs in combined with antidiabetic agents Significant increase in TC was recorded with ACE inhibitors + Metformin, also LDL was increase with ACE inhibitors + insulin while ARBs + Insulin was increase HDL. Serum creatinine increased in both groups used Insulin. ALT was significantly increases with ARBs + Metformin + DPP-4 inhibitors.Electrolytes were affected during the combination with antidiabetic agents, Sodium level was increased with ARBs + Metformin + DPP4 inhibitors and potassium was increase with ARBs + Insulin. Conclusion:There are slight effects on selected biochemical parameters was recorded during the treatment with ACE inhibitors and ARBs separately and when combined with antidiabetic agents.

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Dipeptidyl peptidase-4 (DPP-4) inhibitors constitute an innovative class of oral agents for the treatment of Type 2 Diabetes Mellitus (T2DM). DPP-4 inhibitors increase glucagon-like peptide-1 (GLP-1) availability and correct the "incretin defect" seen in T2DM patients. Peptides derived from collagen have been reported to have DPP-4 inhibitory properties. A double blind randomized trial has been conducted to evaluate the effectiveness of Collagen peptides (CPT) as nutritional supplement in subjects with T2DM. Resistant dextrin (RD), a non-digestible dietary polymer, has been used as active comparator in this study. The clinical study was conducted over a total duration of 12 weeks of treatment period. The study was conducted on 66 enrolled subjects randomized in a 2:2:1:1 ratio as a four arm clinical study design. The subjects consumed either CPT (2.5/5 g) or resistant dextrin (2.5/5 g) for 90 days. The results showed that the consumption of 5 g CPT resulted in significant reduction in fasting blood glucose (FBG) and Glycosylated Haemoglobin (HbA1c) in three months study period in subjects. Insulin sensitivity measured in as HOMA IR has also been improved significantly in the group. Thus this study demonstrates the potential role of CPT as add on nutritional supplement for the management of T2DM.

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