Shakilur Rahman

Irisin as a predictor of glucose metabolism in children: sexually dimorphic effects

Irisin, a novel myokine, increases energy expenditure and glucose tolerance and, thus, improves carbohydrate homeostasis in humans. This hormone has potential therapeutic applications for weight loss and improvement in insulin resistance in subjects with obesity and diabetes mellitus type 2 (T2DM). In this cross‐sectional study, we aimed to associate circulating levels of irisin and several anthropometric and metabolic parameters among Arab children.

Melatonin ameliorates bisphenol A-induced biochemical toxicity in testicular mitochondria of mouse.

Bisphenol A (BPA) is a monomer of polycarbonate plastic used to manufacture plastic baby bottles and lining of food cans. It has endocrine-disrupting potential and exerts both toxic and estrogenic effects on mammalian cells. We studied BPA-induced perturbation of mitochondrial marker enzymes in testes of Swiss albino mice and its amelioration by melatonin. Mice exposed to standardized dose of BPA (10 mg/kg body weight) orally for 14 days showed decrease in activities of marker mitochondrial enzymes such as succinate dehydrogenase, malate dehydrogenase, isocitrate dehydrogenase, monoamine oxidase and NADH dehydrogenase. Besides, it also affected activities of antioxidant enzymes such as superoxide dismutase, glutathione reductase and glutathione peroxidase. BPA also caused lipid peroxidation (LPO) and decrease in reduced glutathione (GSH) content of mitochondria. Concomitant melatonin administration (10 mg/kg body weight; intraperitoneally for 14 days) lowered mitochondrial lipid peroxidation. It also restored the activity of mitochondrial marker enzymes and ameliorated decreased enzymatic and non-enzymatic antioxidants of mitochondria. These results demonstrate that melatonin has a potential role in ameliorating BPA-induced mitochondrial toxicity and the protection is due to its antioxidant property or by the direct free radical scavenging activity.

Does visceral adiposity index signify early metabolic risk in children and adolescents?: Association with insulin resistance, adipokines, and subclinical inflammation

Background:Visceral adiposity index (VAI) is a novel gender-specific index based on waist circumference (WC), BMI, and lipid parameters. Although VAI does not actually estimate visceral adiposity, it accurately reflects visceral fat function and insulin resistance. This index has not been studied in children thus far. This study aims to fill this gap.Methods:In a cohort of Saudi children and adolescents, anthropometric measurements and metabolic/hormonal profile were obtained.Results:A total of 543 subjects, 292 of whom were boys, were included (mean age: 11.9 ± 3.3 y; BMI: 19.8 ± 5.6 kg/m2). In all subjects, VAI was inferior to BMI and WC regarding its correlations with adiponectin, leptin, insulin resistance (homeostasis model of assessment–insulin resistance (HOMA-IR)), C-reactive protein (CRP) level, and systolic blood pressure, but it exhibited a stronger association with glucose in boys (r = 0.23; P < 0.01). In stepwise multivariate analyses, only BMI was consistent as an independent predictor of adiponectin, leptin, HOMA-IR, and CRP. VAI was the only index independently associated with glucose.Conclusion:Although VAI is related to glucose in children, it seems to be inferior to BMI in terms of association with insulin resistance, adipokines, and subclinical inflammation. Until specific studies can be performed in children, VAI should be extrapolated with caution in this age range.

Antiobesity potential of ursolic acid stearoyl glucoside by inhibiting pancreatic lipase

The present study was designed to evaluate the hypolipidemic effect of ursolic acid stearoyl glucoside (UASG) in high-fat diet-induced obesity. Two in vivo experiments such as high-fat diet-induced obesity mice model and lipid emulsion tolerance test in normal rats were performed. In vitro inhibition of pancreatic lipase activity was further measured to substantiate the results. In high-fat diet-induced obesity mice model, female Swiss mice were fed a high fat diet (HFD; 40% fat) with or without 1 or 2% of UASG or 0.012% orlistat for nine weeks. In lipid emulsion tolerance test male Wister rats were orally administered, lipid emulsion with or without 500 or 1000 mg/kg of UASG and the plasma triglycerides were measured from 0.5 to 5 h. Consumption of HFD containing UASG to mice for nine weeks exhibited significant reduction in lipid parameters, body weight, parametrial adipose tissue weight, liver triglyceride (TG) and different organ weight compared to HFD fed control. Further it was noted the improvement in insulin resistance induced by the HFD alone group. Furthermore, consumption of an HFD containing 1 or 2% of UASG significantly increased the fecal content and fecal triglyceride compared with the HFD group. Pre-treatment with UASG inhibited the elevated plasma triglyceride level after the oral administration of the lipid emulsion to rats. Further, UASG significantly inhibits activity of pancreatic lipase at a concentration of 2.5 mg/ml. Data obtained from the results indicated that UASG prevent high-fat diet-induced obesity in mice possibly by inhibiting pancreatic lipase activity.

Habitual Physical Activity is Associated with Circulating Irisin in Healthy Controls but not in Subjects with Diabetes Mellitus Type 2

Irisin, a novel myokine, has been shown to increase following vigorous exercise, with studies suggesting that it mediates some of the beneficial effects of exercise. Irisin might play a role in ‘browning’ of white adipocytes, thus increasing energy expenditure. The role of irisin in exercise and energy expenditure in subjects with diabetes mellitus type 2 (DMT2) remains largely unknown. We aimed to investigate the association between circulating irisin and habitual physical activity in subjects with and without DMT2.

Association of vitamin B12 with pro-inflammatory cytokines and biochemical markers related to cardiometabolic risk in Saudi subjects

Background: This study aimed to examine the relationship between changes in systemic vitamin B12 concentrations with pro-inflammatory cytokines, anthropometric factors and biochemical markers of cardiometabolic risk in a Saudi population. Methods: A total of 364 subjects (224 children, age: 12.99 ± 2.73 (mean ± SD) years; BMI: 20.07 ± 4.92 kg/m2 and 140 adults, age: 41.87 ± 8.82 years; BMI: 31.65 ± 5.77 kg/m2) were studied. Fasting blood, anthropometric and biochemical data were collected. Serum cytokines were quantified using multiplex assay kits and B12 concentrations were measured using immunoassay analyzer. Results: Vitamin B12 was negatively associated with TNF-α (r = −0.14, p < 0.05), insulin (r = −0.230, p < 0.01) and HOMA-IR (r = −0.252, p < 0.01) in all subjects. In children, vitamin B12 was negatively associated with serum resistin (r = −0.160, p < 0.01), insulin (r = −0.248, p < 0.01), HOMA-IR (r = −0.261, p < 0.01). In adults, vitamin B12 was negatively associated with TNF-α (r = −0.242, p < 0.01) while positively associated with resistin (r = 0.248, p < 0.01). Serum resistin was the most significant predictor for circulating vitamin B12 in all subjects (r2 = −0.17, p < 0.05) and in children (r2 = −0.167, p < 0.01) while HDL-cholesterol was the predictor of B12 in adults (r2 = −0.78, p < 0.05). Conclusions: Serum vitamin B12 concentrations were associated with pro-inflammatory cytokines and biochemical markers of cardiometabolic risks in adults. Maintaining adequate vitamin B12 concentrations may lower inflammation-induced cardiometabolic risk in the Saudi adult population.

Circulating betatrophin in healthy control and type 2 diabetic subjects and its association with metabolic parameters

AIMS Betatrophin, a newly identified liver and adipose tissue-derived hormone, has been suggested as an inducer of β-cell proliferation in mice. However, the physiological role of betatrophin remains poorly understood in humans. Hence, the aim of this study was to investigate circulating betatrophin concentrations in normal and type 2 diabetes mellitus (T2DM) Saudi subjects and its association with various metabolic parameters. METHODS In this cross-sectional study, 200 Saudi adults (81 healthy non-T2DM controls, age: 41.43±8.35 [mean±SD]; BMI: 31.58±5.49 and 119 T2DM subjects, age: 48.78±11.76years; BMI: 30.25±4.83kg/m(2)) were studied. Anthropometric and fasting serum biochemical data were collected. Circulating betatrophin was measured using an enzyme-linked immunosorbent assay (ELISA) based kit. RESULTS We observed significantly higher levels of betatrophin in T2DM subjects compared to healthy controls (882.19±329.06 vs 657.14±261.04pg/ml, p<0.001). Furthermore, in T2DM subjects, betatrophin level was positively associated with blood pressure and serum fasting glucose (p<0.05). CONCLUSIONS Our results suggest that circulating betatrophin is significantly elevated in subjects with T2DM compared to healthy controls. Increase in the level of betatrophin in T2DM subjects might be a compensatory mechanism for enhanced insulin demand in T2DM condition.

Protection against tacrolimus-induced cardiotoxicity in rats by olmesartan and aliskiren

Abstract Context: Tacrolimus (TAC), a calcineurin inhibitor, is commonly used as an immunosuppressive agent in organ transplantation, but its clinical use may be limited due to cardiotoxicity. Olmesartan (OLM; angiotensin receptor blocker) and aliskiren (ALK; renin inhibitor) may attenuate cardiotoxicity induced by TAC by inhibition of renin–angiotensin aldosterone system. Objective: The aim of this study was to evaluate the effect of OLM and ALK on TAC-induced cardiotoxicity. Materials and methods: Male Wistar albino rats weighing 200–250 g (10–12 weeks old) were used in this study. Animals were divided into four groups. Group 1 received normal saline, group 2 received TAC (2 mg/kg, intraperitoneally for 14 d), group 3 received OLM (2 mg/kg, p.o. for 28 d) + TAC and group 4 received ALK (50 mg/kg, p.o. for 28 d) + TAC. TAC-induced cardiotoxicity was assessed biochemically and histopathologically. Results: Treatment with OLM or ALK decreased the TAC-induced changes in biochemical markers of cardiotoxicity such as serum aspartate transaminase, creatine kinase and lactate dehydrogenase. OLM or ALK also attenuated the effects of TAC on oxidant–antioxidant parameters such as malondialdehyde, reduced glutathione and catalase. Histopathological and ultrastructural studies showed that OLM or ALK also attenuated TAC-induced cardiotoxicity. Discussion and conclusion: These results suggest that OLM as well as ALK has protective effects against TAC-induced cardiotoxicity; implying that angiotensin receptor blocker or renin inhibitor, respectively, may counteract cardiotoxicity associated with immunosuppressant use.