Aberrant effect of genistein on placenta development expressed through alteration in transforming growth factor-ß1 and alkaline phosphatase across the maternal serum, the placenta and the amniotic fluid.

OBJECTIVES: The mechanism via which genistein, the major isoflavone content of soya, adversely influenced placenta and fetal development was evaluated in pregnant laboratory rats. MATERIALS AND METHODS: There were control, 2 mg/kg and 4 mg/kg genistein groups of rats with five sub-groups based on gestation termination day. At the end of the experiment, animals were sacrificed by CO2 and cervical dislocation, while plasma and serum were processed and stored. The abdomen was opened and the amniotic fluid was siphoned from the uterine sacs, processed and stored. The embryonic implants were excised, the placenta was separated from the fetus and weighed separately. Placenta homogenate was prepared from the harvested placenta, while the rest were processed for histological studies. Transforming growth factor (TGf-ß1) and alkaline phosphatase (ALP) were assayed for in all samples. A significant decrease in the placenta and fetal weights, and a significant decrease in serum and placenta homogenate ALP levels were recorded in genistein groups. RESULTS: There was a reduction in the Trophoblast giant cells population (TGCs). TGCs zone depth, perimeter, and an increase in the placenta and amniotic fluid's TGf-ß1 in all genistein groups at GD-13 towards term, and GD-18 and GD-20, respectively. Maternal plasma TGf-ß1 was increased in 2 mg group early in pregnancy while its level significantly decreased in both 2 mg and 4 mg genistein groups at mid-gestation towards GD-19. CONCLUSION: Genistein aberrant effect on fetal development was via its adverse effect on TGCs proliferation and TGf-ß1 activities in the placenta tissue.

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

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.

Adverse effects of noise stress on glucose homeostasis and insulin resistance in Sprague-Dawley rats.

Noise pollution remains a pervasive health hazard that people encounter especially in large commercial metropolis and has been implicated in many adverse non-auditory health conditions such as hypertension, atherosclerosis, vascular (endothelial) dysfunction and metabolic disorders. There is a growing body of evidence showing that chronic noise exposure is associated with an increased risk of hypercholesterol, adiposity and development of type 2 diabetes. The present study investigated the effect of noise stress on parameters of glucose homeostasis in male rats and possible recovery after noise cessation. Twenty-four (24) adult male Sprague-Dawley rats were designated into four groups (n = 6 per group). All rats except the control group were exposed to 95dB noise using a noise generator for 28 consecutive days. A group of rats was investigated immediately after 28 days of noise exposure (NE28), while others were left to recover from noise stress for 7 days (NER7) or 14 days (NER14). OGTT and ITT were performed using standard methods. Plasma levels of triglyceride (TRIG), total cholesterol (CHOL), low density lipoprotein (LDL) and high-density lipoprotein (HDL) were determined. Serum level of insulin, corticosterone (CORT) and corticosterone-releasing-factor (CRF) were determined using ELISA. Homeostasis model assessment-insulin resistance (HOMA-IR) and glycogen content in liver as well as gastrocnemius muscle were also determined. Although glucose tolerance remained unchanged in the noise-exposed groups, insulin sensitivity was however significantly reduced compared with control. There was significant increase (P < 0.05) in the level of CHOL, LDL and HDL. Noise also increased (P < 0.05) both insulin and CORT levels; and elicited a higher HOMA-IR index in NE28 rats. Hepatic and myocytic glycogen content were lower (P < 0.05) in NE28 rats relative to control. The reported changes above were reversed following a 14-day noise withdrawal period. Noise-induced insulin resistance may result from dysregulation of the stress axis and appears to be reversible with noise cessation.

Glucometabolic effects of single and repeated exposure to forced-swimming stressor in Sprague-Dawley rats.

OBJECTIVES: We aimed to evaluate the effects of a single (acute) and repeated (chronic) exposure to forced-swimming stressor on glucose tolerance, insulin sensitivity, lipid profile and glycogen content in male rats. METHODS: Thirty adult male Sprague-Dawley rats (12 weeks old) were divided randomly into five groups: control group, single exposure (SE) to forced-swim stressor, repeated exposure to forced-swim stressor for 7 days (RE7), 14 days (RE14) and 28 days (RE28). Glucose tolerance test and Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) were undertaken on fasting rats to obtain glucose and insulin profiles. ELISA was performed to assess plasma insulin and corticosterone levels. Total cholesterol, triglyceride, high- and low-density lipoproteins, hepatic and skeletal glycogen content were also determined. RESULTS: Repeated exposure to stressor induced glucose intolerance and insulin resistance in the experimental rats. Results showed that all RE groups exhibited a significantly higher area under the curve compared with others (p=0.0001); similarly, HOMA-IR increased (p=0.0001) in all RE groups compared with control. Prolonged exposure to stressor significantly increased the plasma insulin and corticosterone levels but decreased the glycogen content in the liver and skeletal muscle when compared with the control group. Additionally, chronic stressor significantly increased the total cholesterol and triglyceride levels, however, acute stressor produced significantly elevated high-density lipoproteins level. CONCLUSIONS: In conclusion, repeated exposure to forced-swimming stressor induced glucose intolerance and insulin resistance in rats by disrupting the insulin sensitivity as well as heightening the glycogenolysis in the liver and skeletal muscle. Acute stressor was unable to cause glucose intolerance and insulin resistance but it appears that may have a positive effect on the lipid metabolism.

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

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.

Testosterone promotes glucose intolerance, lipid disorder and oxidative stress in type 1 diabetic rats.

BACKGROUND: A bidirectional relationship has been established between testosterone deficiency (TD) and type 2 diabetes mellitus (T2DM). Low testosterone level has been reported to be a predisposing factor to T2DM, whereas recent clinical studies have shown a high prevalence of low testosterone in diabetic individuals. However, it is not known if any relationship exists between type 1 diabetes mellitus (T1DM) and testosterone level. This study was designed to investigate the effects of TD on T1DM. Twenty-four Sprague-Dawley rats were randomly divided into four groups designated as control, diabetic, orchiectomized and orchiectomized-diabetic. METHODS: Diabetes was induced with an intravenous injection of alloxan, and orchiectomy was done under sterile conditions. Fasting blood glucose (FBG), insulin level, lipid and oxidative parameters were determined in all experimental rats. RESULTS: The area under the curve during oral glucose tolerance test showed that the orchiectomized-diabetic group expressed an enhanced ability to metabolize glucose than the diabetic group. The malondialdehyde level in the diabetic group was significantly higher compared with that in the control and orchiectomized groups. Moreover, there was a significant decrease in glutathione (GSH) activity and an increase in superoxide dismutase activity in the diabetic group compared with control. Meanwhile, the activities of GSH and catalase were significantly reduced in the orchiectomized as well as the orchiectomized-diabetic group when compared with both control and diabetic groups. CONCLUSIONS: These data indicate that TD attenuates glucose intolerance under diabetic conditions and is equally associated with a considerable reduction in oxidative stress, which implies that testosterone may be a pro-oxidant.

Effect of methanol extract of Ricinus communis seed on reproduction of male rats.

AIM: To investigate the effect of methanol extract of Ricinus communis seed (RCE) on male rats reproductive functions. METHODS: Thirty-two male albino rats were divided into four groups. Groups 1, 2 and 3 were gavaged with 0.2 mL of 2.5% tween 80 (RCE vehicle; control) or 20 mg/(kg x d) and 40 mg/(kg x d) of RCE, respectively, for 30 days, and group 4 was also gavaged with 40 mg/(kg x d) of RCE, but was allowed a recovery period of 30 days. Five untreated female rats were cohabited with male rats in each group from day 25 of RCE treatment for 5 days, except group 4, where cohabitation began on day 25 of the recovery period. All male rats were sacrificed 24 h after the experiments. The female rats were laparotomized on day 19 of pregnancy and the number and weight of litters were recorded. RESULTS: There was a significant decrease (P<0.01) in the weight of the reproductive organs, sperm functions and serum levels of testosterone in RCE treated rats. There was disorganization in the cytoarchitecture of the testes, disruption of the seminiferous tubules and erosion of the germinal epithelium. The number and weight of litters of rats in groups 2 and 4 decreased significantly (P<0.05) but no changes were observed in group 3. RCE caused no changes in liver, kidney, heart or body weights in male rats. CONCLUSION: RCE has a reversible negative impact on male reproductive functions, which appears to be mediated via gonadal disruption in testosterone secretion.