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El Mesallamy H.O.,Ain Shams University | Hamdy N.M.,Ain Shams University | Mostafa D.M.,Ain Shams University | Amin A.I.,National Institute of Diabetes and Endocrinology NIDE
Journal of Interferon and Cytokine Research | Year: 2014

Chronic inflammation and insulin resistance form hallmarks of type 2 diabetes mellitus (T2DM). An increased circulating level of the serine protease granzyme B (GzmB) is observed during prolonged inflammation and is implicated in the pathogenesis of several chronic inflammatory diseases. Moreover, insulin receptor cleavage by unknown proteases, yielding elevated levels of insulin receptor α-subunit (IRα), was observed in T2DM and was proposed as a new mechanism of insulin resistance. Therefore, a possible association between GzmB and IRα is suggested. Accordingly, this study was set to explore whether GzmB and IRα levels are altered in T2DM patients with the impact of obesity. Furthermore, we aimed to identify if GzmB contributes towards inflammation and insulin resistance through its suggested extracellular activities. All subjects were assessed for anthropometric and metabolic parameters related to obesity and T2DM. In addition, fasting plasma insulin, GzmB, interleukin-1β (IL-1β), and IRα levels were estimated by enzyme linked immunosorbent assay. Levels of GzmB and IRα were found to be significantly elevated in T2DM patients compared to nondiabetic subjects. In addition, GzmB levels were positively correlated with measures of obesity and insulin resistance, IL-1β, IRα, and other metabolic parameters. While multiple linear regression analysis revealed that both T2DM and central obesity were predicting factors for GzmB, our findings reveal a possible role of GzmB in T2DM. © Mary Ann Liebert, Inc.


Noureldein M.H.,Ain Shams University | Abd El-Razek R.S.,Ain Shams University | El-Hefnawy M.H.,National Institute of Diabetes and Endocrinology NIDE | El-Mesallamy H.O.,Ain Shams University
Diabetes Research and Clinical Practice | Year: 2015

Aims: The aim of the current study is to investigate the effect of fenofibrate alone and in combination with pioglitazone on serum sirtuin 1 and fetuin A of obese patients with Type 2 Diabetes Mellitus (T2DM). MethodsIntervention effect on inflammatory parameters was assessed before and after treatment. The study was conducted on 60 postmenopausal females of whom, only 44 patients completed the study. They were distributed as follows; obese patients without T2DM (n= 15) who administered fenofibrate (160. mg/day) once for 8 weeks, obese patients with T2DM (n= 15) who administered fenofibrate (160. mg/day) once for 8 weeks, obese patients with T2DM (n= 14) who administered fenofibrate (160. mg/day) and pioglitazone (15. mg/day) combination once for 8 weeks.We measured fasting plasma glucose, glycated hemoglobin (HbA1c), serum lipids. Inflammatory markers (high sensitivity C-reactive protein "hs-CRP", interleukin-6 "IL-6", fetuin A, and sirtuin 1) of patients were measured in serum using enzyme-linked immunoassay (ELISA) kits. ResultsSirtuin 1 levels in obese patients with T2DM were significantly lower than its levels in obese patients while fetuin A levels were significantly higher (P<. 0.001). Fenofibrate, alone and in combination with pioglitazone, significantly decreased triacylglycerol, hs-CRP, IL-6, fetuin A and increased sirtuin 1 levels (P<. 0.001) which suggests that it can be used to delay the complications of obesity and T2DM. There is a strong correlation between fetuin A, sirtuin 1, IL-6 and hs-CRP levels suggesting a shared common pathway. ConclusionsFenofibrate was shown to increase serum sirtuin 1 and decrease serum fetuin A levels in obese patients. Trial numberPACTR201407000856135. © 2015 Elsevier Ireland Ltd.


El-Mesallamy H.O.,Ain Shams University | Kassem D.H.,Ain Shams University | El-Demerdash E.,Ain Shams University | Amin A.I.,National Institute of Diabetes and Endocrinology NIDE
Metabolism: Clinical and Experimental | Year: 2011

Recently, vaspin and visfatin/Nampt have been identified as interesting novel adipokines having insulin-sensitizing and insulin-mimetic effects, respectively. However, the relationship between them has not been elucidated; and their circulating levels in type 2 diabetes mellitus (T2DM) have not been adequately studied. Therefore, this study was designed to investigate whether their levels are altered in Egyptian T2DM patients and to study the correlation of these novel adipokines with each other and with insulin resistance, interleukin-6 (IL-6), and other biochemical parameters. The levels of vaspin, visfatin/Nampt, IL-6, insulin, and other parameters were measured in nonobese and obese T2DM patients together with matched healthy nondiabetic control subjects. Vaspin, visfatin/Nampt, and IL-6 levels were measured by enzyme-linked immunosorbent assay, whereas insulin levels were measured by chemiluminescence technique. Vaspin and visfatin/Nampt levels were found to be significantly elevated in nonobese (1.62 ± 0.22 and 25.9 ± 3.44 ng/mL, respectively) and obese T2DM patients (2.76 ± 0.38 and 45.4 ± 4.60 ng/mL, respectively) compared with control subjects (0.42 ± 0.05 and 9.37 ± 1.98 ng/mL, respectively) at P < .01. In addition, vaspin and visfatin/Nampt levels were found to be significantly positively correlated with each other and with other biochemical parameters. In conclusion, both vaspin and visfatin/Nampt might play an important role in the pathogenesis of T2DM. In addition, the 3 adipokines-vaspin, visfatin/Nampt, and IL-6-are significantly interrelated with each other. Other possible mechanisms of action for vaspin should be considered besides the inhibition of unknown substrate proteases. © 2011 Elsevier Inc. All rights reserved.


El-Mesallamy H.O.,Ain Shams University | Mostafa A.M.,Ain Shams University | Amin A.I.,National Institute of Diabetes and Endocrinology NIDE | El Demerdash E.,Ain Shams University
Diabetes Research and Clinical Practice | Year: 2011

Recently, YKL-40 has been identified as a new inflammatory marker of type 2 diabetes mellitus (T2DM), while leptin is one of the most important adipose derived hormones. However, the relationship between them has not been elucidated. Therefore this study aimed to study their correlation in obese T2DM patients. © 2011 Elsevier Ireland Ltd.


Aboouf M.A.,Ain Shams University | Hamdy N.M.,Ain Shams University | Amin A.I.,National Institute of Diabetes and Endocrinology NIDE | El-Mesallamy H.O.,Ain Shams University
Diabetes Research and Clinical Practice | Year: 2015

Highlights: Aims: Apelin is one of adipokines that plays a pivotal role in energy metabolism, insulin sensitivity and vascular integrity. A definite genetic variant of apelin gene (APLN), rs3115757, was recently introduced to potentially influence apelin expression in adipocytes. The aim of our study was to explore the sights of a potential association of this functional variant with obesity traits, insulin resistance indices as well as type 2 diabetes mellitus (T2DM) prevalence. Methods: Genotype screening for rs3115757 variant in 151 Egyptian female samples was conducted. Fasting levels of serum insulin and lipid profile, in addition to plasma glucose were measured. Cochran-Armitage trend test was used to decide the risk allele and evaluate the association between the candidate variant and obesity using a case-control design. Results: The homozygous G risk allele carriers showed higher values of body mass index (BMI) and waist circumference (P=0.001,0.02, respectively) as compared to CC or CG genotypes. As for GG genotype carriers, the risk of developing morbid obesity in lean subjects, (BMI. <. 25), is twelve times the risk in subjects carrying other genotypes (OR. =12.09, 95% CI: 1.4, 104.8, P=0.024). On the other hand, GG carriers are shown to be more resistant to insulin. Significantly after correction for BMI and age effects, GG genotype carriers showed 14% and 41% increment in insulin level and resistance (OR. =1.14, 95% CI: 1.06, 1.23, P=0.001), (OR. =1.42, 95% CI: 1.19, 1.70, P<. 0.001), respectively. Conclusion: These results suggest a prospective role mediated by this variant in mounting obesity disorders and as significant as insulin resistance complications. © 2015 Elsevier Ireland Ltd.

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