Titilola Samuel

Niacin improves adiponectin secretion, glucose tolerance and insulin sensitivity in diet-induced obese rats

Abstract The present study examined the effect of dietary niacin supplementation on fat mass, glucose control, insulin sensitivity, lipid profile, and adiponectin level in diet-induced obese rats. Male Sprague-Dawley rats (n = 21) were initially divided into 2 groups of seven and fourteen rats; the group of 14 rats was fed with a high-fat diet (HFD) and the other group of 7 rats consumed the control diet. Eight weeks after the diet regimen started, half of the rats from the HFD group were shifted to the niacin-supplemented diet (HFND; 1 mg niacin/kg diet) while the remaining rats continued on the HFD for another 6 weeks. Results obtained showed that HFD-fed obese rats exhibited significant increase in body weight gain, reduced glucose tolerance, insulin sensitivity and increased adiposity, as well as altered lipid profile after 8 weeks of feeding compared with the controls. However, niacin-supplemented rats showed reduced weight gain and body weight compared with HFD-induced obese rats even in the absence of a significant difference in the food intake among the groups in the experiment. In addition, the rats showed an improved time-course glucose control and insulin sensitivity as demonstrated by a significantly lower area under curve (AUC) values for the glucose curves. The plasma levels of cholesterol, triglycerides and low density lipoprotein (LDL) returned towards control values in rats supplemented with niacin compared with obese rats. The findings suggest that niacin exerts beneficial effect on adiposity, glucose tolerance and insulin sensitivity, and plasma lipids, and that it specifically modulates the level of serum adiponectin under obese condition.

A comparison of the anti-diabetic potential of d-ribose-l-cysteine with insulin, and oral hypoglycaemic agents on pregnant rats

Graphical abstract

Dynamics of inflammatory reaction and oxidative stress across maternal serum, placenta and amniotic fluid in laboratory rats and the role played by genistein aglycone

Abstract Background Genistein was reported to adversely influence fetal development although this is yet to be fully understood as a mechanism. Methods In this study, pregnant rats were divided into control (Cont.) and genistein force-fed (2-mg/kg and 4-mg/kg) groups. Each group was divided further into five subgroups: GD-0, GD-6, GD-13, GD-18, and GD-20 based on the terminal gestational day (GD). On the respective terminal GD, the rats were sacrificed and blood samples and amniotic fluid were carefully collected and separated and placenta homogenates were prepared. These samples were evaluated for oxidative stress and inflammatory reaction. The weights of embryonic implant and placenta tissue were also recorded. Heat shock protein (Hsp) (60 and 90), corticosterone, and oxidative stress biomarkers were determined in all the samples. Results Fetal and placental weights in all genistein-exposed groups were significantly decreased. A fluctuation in the level of the Hsp was recorded with a significant decrease recorded in Hsp90 level in the placenta and amniotic fluid towards GD-20 along with a concomitant increase in the corticosterone level in the amniotic fluid in all genistein groups compared to control. Maternal serum at GD-18 and GD -20 recorded a significant increase in antioxidant level (SOD, GSH, CAT) in all genistein-exposed groups. However, these antioxidants were significantly reduced in the placenta and the amniotic fluid compared to control. Conclusions Genistein enhances the placenta function in attenuating the risk of oxidative stress in the amniotic fluid and deferentially suppressed inflammatory activities in the placenta during early gestation and towards late gestation period.

High-Dose Perinatal Folic-Acid Supplementation Alters Insulin Sensitivity in Sprague-Dawley Rats and Diminishes the Expression of Adiponectin

ABSTRACT The possible intake of folate in excess of the recommended upper levels is a matter of critical importance. This study was conducted to investigate the effects of prenatal and postnatal high folic acid supplementation (FAS) on glucose tolerance, insulin sensitivity, lipid metabolism, and expression of adiponectin in rats. The study included 20 female rats divided into two groups: control group and FAS group (receiving high folic acid supplemented diet). Both groups of female rats were mated and pregnancy confirmed. At parturition, the diet of 5 dams that were fed with control diet during gestation and their litters was changed to FAS diet and continued throughout lactation. Similarly, half of the dams that were previously fed with FAS diet during gestation and their litters were also changed to control diet. The remaining 5 dams in each group continued on their respective diets throughout lactation with their litters. Other dams remained on their respective diets throughout lactation. Food and water intake, body weight, lipid concentrations, insulin, and the expression of adiponectin were determined. Glucose tolerance and insulin sensitivity were also measured to evaluate glucose homeostasis. FAS significantly increased the postweaning food, water intake, triglyceride, and insulin levels but diminished insulin sensitivity in adult offspring. The expression of adiponectin in insulin-sensitive tissues was also significantly decreased and these were consistent with insulin resistance of FAS offspring. High-dose FAS may promote insulin resistance and dyslipidemia and disrupt glucose metabolism possibly by depressing adiponectin expression. Although this is an animal model and the effects of the diets cannot be directly transposed to humans, this study provides indications of the possible adverse effects of FAS maternal diet on glucose metabolism in the offspring.

Genetic Polymorphisms of Glucose-6-Phosphate Dehydrogenase in Lagos, Nigeria

Abstract Glucose-6-phosphate dehydrogenase (G6PD) is an essential enzyme in the pentose phosphate pathway that prevents oxidative damage to cells. This study determined the genotypic and allelic frequencies of G6PD G202A and A376G and also investigated correlation between G6PD polymorphisms and hemoglobin (Hb) phenotypes in children in Lagos, Nigeria. Seventy-eight children [55 with Hb AA (βΑ/βA) and 23 with Hb AS (βΑ/βS) trait] and 65 Hb SS (βS/βS) (HBB: c.20A>T) subjects in steady state with age range between 5–15 years were recruited for the study. Hemoglobin phenotypes of all study participants were carried out using alkaline electrophoresis and solubility tests. Genomic DNA was extracted from whole blood and restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) was used to determine the G202A and the A376G mutations of the G6PD gene. The genotype and allele distributions of G6PD G202A and A376G according to the Hb phenotypes were not statistically significant (p > 0.05). The minor allele frequency 202A was 0.15 (15.0%) and 0.14 (14.0%) in cases and controls, respectively. The overall frequency of 376G allele in the case group was 0.35 (35.0%) and 0.38 (38.0%) in the control group. No statistical significance was observed in the genotype and allele distributions of A376G in both the case and control groups (p > 0.05). The G6PD A− frequency in Hb SS subjects and the control group were 6.2 and 2.6%, respectively. G6PD G202A and A376G polymorphisms were not associated with Hb phenotypes and the allele distributions of 202A and 376G in this study are typical of West African populations.

Magnesium upregulates insulin receptor and glucose transporter-4 in streptozotocin-nicotinamide-induced type-2 diabetic rats

Abstract Objective. We investigated the effects of magnesium supplementation on glucose tolerance, insulin sensitivity, oxidative stress as well as the concentration of insulin receptor and glucose transporter-4 in streptozotocin-nicotinamide induced type-2 diabetic (T2D) rats. Methods. Rats were divided into four groups designated as: 1) control (CTR); 2) diabetic untreated (DU); 3) diabetic treated with 1 mg of Mg/kg diet (Mg1-D); and 4) diabetic treated with 2 mg of Mg/kg diet (Mg2-D). T2D was induced with a single intraperitoneal (i.p.) injection of freshly prepared streptozotocin (55 mg/kg) aft er an initial i.p. injection of nicotinamide (120 mg/kg). Glucose tolerance, insulin sensitivity, lipid profile, malondialdehyde (MAD) and glutathione content, insulin receptors (INSR) and glucose transporter-4 (GLUT4), fasting insulin and glucose levels were measured, and insulin resistance index was calculated using the homeostatic model assessment of insulin resistance (HOMA-IR). Results. Magnesium supplementation improved glucose tolerance and lowered blood glucose levels almost to the normal range. We also recorded a noticeable increase in insulin sensitivity in Mg-D groups when compared with DU rats. Lipid perturbations associated T2D were significantly attenuated by magnesium supplementation. Fasting glucose level was comparable to control values in the Mg-D groups while the HOMA-IR index was significantly lower compared with the DU rats. Magnesium reduced MDA but increased glutathione concentrations compared with DU group. Moreover, INSR and GLUT4 levels were elevated following magnesium supplementation in T2D rats. Conclusion. These findings demonstrate that magnesium may mediate effective metabolic control by stimulating the antioxidant defense, and increased levels of INSR and GLUT4 in diabetic rats.

Abstract 4456: Preliminary investigation of the promoter methylation status of BRCA1, BRCA2, TP53 genes of some breast cancer patients

Epigenetic alterations in BRCA1, BRCA2 and TP53, such as DNA methylation, may be an effective approach in diagnosis, prognosis and therapy in breast cancer. This study examines the DNA methylation signature of BRCA1, BRCA2 and TP53 in some breast cancer patients attending a Clinic in Lagos, Nigeria. In this study, 14 blood specimens with Invasive Ductal Carcinoma (IDC) were investigated. The samples were modified by Bisulfite modification, and then assessed by Methylation-Specific PCR (MSP). The methylation analysis indicates that 7(50%) of the 14 patients had a segment of the promoter region of BRCA1 gene methylated, 8 (57.14%) of BRCA2 methylated and 11(78.57%) of TP53 promoter region. This study provides preliminary evidence for the gene expression inactivation of BRCA 1, BRCA 2, and TP53 Genes in over 50% of the 14 patients with Stage 2 invasive ductal carcinoma who participated in this study. Citation Format: Titilola A. Samuel, babatunde ayo james, Muhammad HABEEB, temitope oshodi, olubunmi magbagbeola. Preliminary investigation of the promoter methylation status of BRCA1, BRCA2, TP53 genes of some breast cancer patients. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4456.

3 Intrasound Therapy Reverses The Effects Of Alcohol Consumption On The Healing Tendon And Augments Healing

Functional abnormalities in wound structure has been identified as a potential complication if a patient consumes alcohol prior to injury and studies suggest that even a single incidence of acute ethanol exposure can perturb the tissue response to trauma significantly. Ethanol ingestion has been shown to result in delayed and abnormal tendon healing 3 weeks after injury. This study investigated the effects of low intensity intrasound therapy (LITR) given twice daily on the morphology and antioxidant parameters in the healing tendon following an acute injury in rats exposed to prior ethanol consumption. Fifteen male rats, randomised into three groups all underwent induced crush injury to the Achilles tendon. Groups 2 and 3 had prior administration of 30% ethanol for six days. The three groups were allocated to: serve as controls (Group 1), received no treatment (Group 2), LITR twice daily (Group 3). LITR was commenced immediately post-injury and was given twice daily over the first 6 days. The animals were sacrificed on day 20 post-injury and the tendons were excised, and processed for histology and anti-oxidant and MDA assay. The tendons in group 2 showed disordered and haphazard collagen formation with neutrophilic infiltrates and high tenoblast population at 20 days post-injury while the LITR treated tendon had dense, well-ordered, parallel collagen deposits with fewer tenoblasts. LITR also significantly improved the antioxidant parameters and lowered the MDA compared with the alcohol-exposed untreated tendon (p < 0.05). LIRT thus reverses the deleterious effect of ethanol on the healing tendon and resulted in near-normal morphology of the healing tendon 20 days post-injury. Abstract 3 Figure 1 L/S of tendon of rat. A: control, B: alcohol fed with no treatment and C: alcohol fed and treated with LITR. (H&E) X200. A shows moderately aligned collagen fibres (C), B shows disorganized collagen fibres (C) with neutrophilic infiltrates (N) while C shows orderly and parallel collagen deposits (C) and elongated tenocytes (T) Abstract 3 Table 1 Correlation of antioxidants with MDA Spearman’s Correlation (r) Groups SOD Catalase GRP 1 -0.63 -0.63 GRP 2 0.37 0.37 GRP 3 -0.98 -0.97 Group 1: Control (Nil alcohol, nil treatment) Group 2: Alcohol, nil treatment Group 3: Alcohol, LITR twice daily Abstract 3 Table 2 Population of tendon cells Total number of cells (N)/Unit Area Groups TB TC Ratio of TB to TC p-value X ± SD X ± SD GRP 1 710 ± 353 334 ± 120 2 : 1 0.12 GRP 2 693 ± 206 210 ± 52 3 : 1 0.02* GRP 3 572 ± 385 445 ± 76 1: 1 0.59 TB: Tenoblasts; TC: Tenocytes Group 1: Control (Nil alcohol, nil treatment) Group 2: Alcohol, nil treatment Group 3: Alcohol, LITR twice daily * Significant at p < 0.05 References Aiyegbusi et al . Connective Tissue Research. 2012;53(6):478–484 Novasonic. www.novasonicwest.com/novasonic. 2007 Molina et al. Alcohol Clin Exp Res. 2002;26(1):120–8 Sommers MS. Crit Care Nurse. 1994;14:82–86, 88–93