The effect of intra-nasal co-treatment with insulin and growth factor-rich serum on behavioral defects, hippocampal oxidative-nitrosative stress, and histological changes induced by icv-STZ in a rat model.

Impaired insulin and growth factor functions are thought to drive many alterations in neurodegenerative diseases like dementia and seem to contribute to oxidative stress and inflammatory responses. Recent studies revealed that nasal growth factor therapy could induce neuronal and oligodendroglia protection in rodent brain damage induction models. Impairment of several growth factors signaling was reported in neurodegenerative diseases. So, in the present study, we examined the effects of intranasal co-treatment of insulin and a pool of growth factor-rich serum (GFRS) which separated from activated platelets on memory, and behavioral defects induced by intracerebroventricular streptozotocin (icv-STZ) rat model also investigated changes in the hippocampal oxidative-nitrosative state and histology. We found that icv-STZ injection (3 mg/kg bilaterally) impairs spatial learning and memory in Morris Water Maze, leads to anxiogenic-like behavior in the open field arena, and induces oxidative-nitrosative stress, neuroinflammation, and neuronal/oligodendroglia death in the hippocampus. GFRS (1µl/kg, each other day, 9 doses) and regular insulin (4 U/40 µl, daily, 18 doses) treatments improved learning, memory, and anxiogenic behaviors. The present study showed that co-treatment (GFRS + insulin with respective dose) has more robust protection against hippocampal oxidative-nitrosative stress, neuroinflammation, and neuronal/oligodendroglia survival in comparison with the single therapy. Memory and behavioral improvements in the co-treatment of insulin and GFRS could be attributed to their effects on neuronal/oligodendroglia survival and reduction of neuroinflammation in the hippocampus.

In Vitro and In Vivo Improvement of Islet Quality and Transplantation Successes following Islet Treatment with Biomaterials in Diabetic Rats.

Background: Loss of islet survival and function, caused by native niche disruption and oxidative stress induction during mechanical and enzymatic isolation, limits the effectiveness of islet transplantation. Reconstitution of islet microenvironment, vascularization, and decreased oxidative stress with biomaterials may improve islet quality and graft outcomes. We investigated effects of two biomaterials, platelet-rich plasma and pancreatic islets homogenate combination on islet recovery and quality by evaluating in vitro islet survival, secretory function, and oxidative stress parameters and assessing in vivo transplantation outcomes. Methods: In vitro, islet viability and secretory function of isolated islets were assessed after 24 h and 72 h incubation with biomaterials. Also, oxidative stress markers were measured once after isolation and 24 h after incubation with biomaterials. For evaluating in vivo effects, cultured islets for 24 h were transplanted into subscapular space of diabetic rat kidney, and outcomes were analyzed by measuring serum glucose and insulin concentrations, glucose tolerance test, level of oxidative parameters, and pancreatic gene expression. Results: Treating islets with biomaterials significantly increased their viability and secretory function, reduced MDA level, and elevate SOD and CAT activity. Decreased level of glucose and MDA improved insulin level, increased SOD activity, and also enhanced pdx1 and insulin gene expression in diabetic rats after islet transplantation. Conclusions: Biomaterials used in the present study should be consider as beneficial materials for increasing islet transplantation outcome. These materials may hamper transplantation limitation to some extent.

Neuroprotective Effect of Wharton's Jelly-Derived Mesenchymal Stem Cell-Conditioned Medium (WJMSC-CM) on Diabetes-Associated Cognitive Impairment by Improving Oxidative Stress, Neuroinflammation, and Apoptosis.

According to strong evidence, diabetes mellitus increases the risk of cognitive impairment. Mesenchymal stem cells have been shown to be potential therapeutic agents for neurological disorders. In the current study, we aimed to examine the effects of Wharton's jelly-derived mesenchymal stem cell-conditioned medium (WJMSC-CM) on learning and memory, oxidative stress, apoptosis, and histological changes in the hippocampus of diabetic rats. Randomly, 35 male Sprague Dawley rats weighing 260-300 g were allocated into five groups: control, diabetes, and three diabetic groups treated with insulin, WJMSC-CM, and DMEM. The injections of insulin (3 U/day, S.C.) and WJMSC-CM (10 mg/week, I.P.) were done for 60 days. The Morris water maze and open field were used to measure cognition and anxiety-like behaviors. Colorimetric assays were used to determine hippocampus glutathione (GSH), malondialdehyde (MDA) levels, and antioxidant enzyme activity. The histopathological evaluation of the hippocampus was performed by Nissl staining. The expression levels of Bax, Bcl-2, BDNF, and TNF-α were detected by real-time polymerase chain reaction (RT-PCR). According to our findings, WJMSC-CM significantly reduced and increased blood glucose and insulin levels, respectively. Enhanced cognition and improved anxiety-like behavior were also found in WJMSC-CM-treated diabetic rats. In addition, WJMSC-CM treatment reduced oxidative stress by lowering MDA and elevating GSH and antioxidant enzyme activity. Reduced TNF-α and enhanced Bcl-2 gene expression levels and elevated neuronal and nonneuronal (astrocytes and oligodendrocytes) cells were detected in the hippocampus of WJMSC-CM-treated diabetic rats. In conclusion, WJMSC-CM alleviated diabetes-related cognitive impairment by reducing oxidative stress, neuroinflammation, and apoptosis in diabetic rats.

Effect of methamphetamine on ultraweak photon emission and level of reactive oxygen species in male rat brain.

All living cells, including neurons, generate ultra-weak photon emission (UPE) during biological activity, and in particular, in the brain, it has been shown that UPE is correlated with neuronal activity and associated metabolic processes. Various intracellular factors, as well as external factors, can reduce or increase the intensity of UPE. In this study, we have used Methamphetamine (METH) as one potentially effective external factor, which is a substance that has the property of stimulating the central nervous system. METH can impair mitochondrial function by causing toxicity via various pathways, including an increase in the number of mitochondria, hyperthermia, the increased metabolic activity of the brain, and the production of glutamate and excess calcium. In addition to mitochondrial dysfunction, METH alters cellular homeostasis, leading to cell damage and the production of excess ROS. The aim of this study is to measure and compare the UPE intensity and reactive oxygen species (ROS) levels of the prefrontal, motor, and visual cortex before and after METH administration. Twenty male rats were randomly assigned to two groups, the control, and METH groups. In the control group, 2 h after injection of normal saline and without any intervention, and in the experimental group 2 h after IP injection of 20 mg/kg METH, sections were prepared from three areas: prefrontal, motor, and V1-V2 cortex, which were used to evaluate the emission of UPE using a photomultiplier tube (PMT) device and to evaluate the amount of ROS. The results showed that the amount of ROS and UPE in the experimental group in all three areas significantly increased compared to the control group. So, METH increases UPE and ROS in the prefrontal, motor, and visual regions, and there is a direct relationship between UPE intensity and ROS production. Therefore, UPE may be used as a dynamic reading tool to monitor oxidative metabolism in physiological processes related to ROS and METH research. Also, the results of this experiment may create a new avenue to test the hypothesis that the excess in UPE generation may lead to the phenomenon of phosphene and visual hallucinations.

The Effect of Hydroalcoholic Calendula Officinalis Extract on Androgen-Induced Polycystic Ovary Syndrome Model in Female Rat.

Background: Polycystic ovary syndrome (PCOS) is the most common hormonal disorder in women of reproductive age, and the major cause of infertility. Today, using medicinal plants instead of chemical drugs could be an alternative treatment option for PCOS. The purpose of this study was to determine the effect of Calendula officinalis hydroalcoholic extract on PCOS in rats. Method: 60 female adult rats were randomly divided into six groups, including control, sham, PCOS group, and treated PCOS groups receiving hydroalcoholic extract of Calendula officinalis with different dosages of 200, 500, and 1000 mg/kg. PCOS was induced by subcutaneous injection of DHEA 6 mg/100 g bw for 35 days. For two weeks, the extract was taken orally. The serum glucose, insulin, sex hormone levels, and oxidative status were measured at the end of the experiment. The ovaries were dissected for histomorphometric and pathological analysis. Results: When compared to the control and sham groups, the PCOS group showed a significant increase in glucose, insulin, testosterone, and malondialdehyde (MDA) concentrations, cystic and atretic follicles, and thickness of the theca and tunica albuginea layers, and a significant decrease in LH concentration, total antioxidant capacity, corpus luteum, antral follicles, and oocyte diameter. The mean concentration of FSH, on the other hand, did not change significantly. A trend of improvement was found in the treated groups with high doses of Calendula officinalis extract. Conclusion: In rats with PCOS and nonovulation, Calendula officinalis hydroalcoholic extract improved oxidative stress, restored folliculogenesis, and increased ovulation.

Cotransplant With Pancreatic Islet Homogenate Improved Survival and Long-Term Efficacy of Islet Transplant in Streptozotocin-Diabetic Rats.

OBJECTIVES: Pancreatic islet transplant is suggested as a promising treatment option in diabetes, but the number of viable and functional islets and the long-term efficacy of transplanted islets have not been satisfactory. Islet isolation leads to destruction of the extracellular matrix and loss of trophic support of islets, which reduces their survival and function. Reconstruction of islet microenvironment with biomaterials may preserve islet survival and graft efficacy. Accordingly, we investigated the effects of pancreatic islet homogenate on islet quality and graft outcomes in diabetic rats. MATERIALS AND METHODS: Islets were isolated from the pancreas of Sprague Dawley rats and were cultured with or without pancreatic islet homogenate. Before transplant, viability, insulin content, and insulin released from cultured islets were assessed. Islets were then transplanted into subcapsular space of diabetic rat kidney. Transplant outcomes were evaluated by plasma glucose and insulin levels, glucose tolerance tests, and stress oxidative markers. RESULTS: Viability and insulin release in the pancreatic islet homogenate-treated islets were significantly higher than that in the control islets. After transplant of islets, recipient rats with pancreatic islet homogenate showed significant decreases in blood glucose and malondialdehyde levels and increases in superoxide dismutase activity and plasma insulin levels. CONCLUSIONS: Islet treatment with pancreatic islet homogenate could improve islet survival and transplant function and outcomes. Oxidative stress reduction might be a secondary beneficial effect of improved quality of treated islets.

Curcumin can prevent the loss of sinoatrial node cells in methionine-treated rats: A stereological study.

Methionine (MET) rich diets, smoking, coffee and alcohol consumption, low physical activity, and aging are related to high plasma concentrations of homocysteine, which can jeopardize the heart health. Although hyperhomocysteinemia has been considered a recognized risk factor for cardiac dysrhythmia, the structural changes of the conductive system, including Sinoatrial (SA) node of the heart involved in the disorder, have not been completely clarified. Curcumin is the main component of turmeric and has shown some cardioprotective effects. This study aimed to evaluate the effect of curcumin on the structural changes of the SA node in L-MET-treated rats. These alterations were evaluated by means of stereological techniques, namely cavalieri principle for volume estimation and optical disector counting technique for cell counting. Both techniques used two-dimensional images for obtaining three-dimensional parameters. The rats were divided into four groups, including control, MET-treated (1 g/kg/day), curcumin-treated, (100 mg/kg/day), and MET + curcumin. The treatments were performed for 28 days. On the final day, SA nodes were dissected out for stereological investigation. Compared to the control rats, the volume of SA node, total volume of grape-like cell clusters, and number of SA node cells were respectively decreased by 42%, 34%, and 37% in the MET-treated group (p < 0.04). However, collagen density remained constant in all the study groups. Furthermore, treatment with curcumin could protect the SA node from cellular decline in the MET + curcumin group (p < 0.01). It can be concluded that curcumin could prevent the structural changes of the SA node in the rats treated with methionine.

Time-dependent effects of platelet-rich plasma on the memory and hippocampal synaptic plasticity impairment in vascular dementia induced by chronic cerebral hypoperfusion.

The present study aimed to investigate the effects of early and late administration of platelet-rich plasma (PRP) on learning-memory and hippocampal synaptic plasticity impairment in rat model of vascular dementia. Sprague-Dawley rats (6-7 weeks) were randomly divided into control, sham, 2VO + V (bilateral carotid vessel occlusion + vehicle), 2VO + E-PRP (early after 2VO), and 2VO + L-PRP (late after 2VO) groups. The injection of PRP started immediately or on the day 20 after 2VO in 2VO + E-PRP and 2VO + L-PRP, respectively, and continued until 28th day (two-time a week). The passive avoidance and Morris water maze tests were used for evaluation of fear and spatial memory formation. The in-vivo long-term potentiation (LTP) was evaluated by field-potential recording, paired-pulse ratio (PPR) and input-output (I/O) curve which were monitored as indexes for evaluation of short-term plasticity (STP) and basal-synaptic transmission (BST), respectively. The 2VO decreased PPR at inter-stimuli interval (ISI) 10 ms and BST, but injection of PRP in both treated groups rescued the PPR and BST depression. In addition, the induction of LTP, fear and spatial memory performance decreased in the 2VO + V group. However, early treatment, but not late, recovered LTP and memory. The PPR and BST improved with early and late treatment; therefore, the number and time of injection seem to be not important for recovery of BST. However, we found that LTP and memory loss rescued only with early administration. Hence, timely injection, before development of the disease, or number of injections could be critical.

Improving effect of combined inorganic nitrate and nitric oxide synthase inhibitor on pancreatic oxidative stress and impaired insulin secretion in streptozotocin induced-diabetic rats.

PURPOSE: The aim of this study was to evaluate the effect of dietary nitrate on secretory function of pancreatic islet and oxidative stress status in streptozotocin (STZ) induced type 1 diabetes in absence or presence of nitric oxide synthase inhibitor (L-NAME). METHODS: Fifty adult male sprague-dawly rats were divided into 5 groups: controls (C), diabetes (D), diabetes+nitrate (DN), diabetes +L-NAME (D + Ln), and diabetes+nitrate+L-NAME (DN + Ln) for 45 days. The concentrations of sodium nitrate and L-NAME were respectively 80 mg/L in drinking water and 5 mg/kg intraperitoneally. Body weight gain, plasma levels of glucose and insulin, islet insulin secretion and content, lipid peroxidation and antioxidant status in the pancreas of rats were determined. RESULTS: Compared to control group, the body weight gain and plasma insulin level were significantly decreased and plasma glucose and pancreatic NO and MDA concentrations and antioxidant enzymes activities were significantly increased in the STZ diabetic rats. In the diabetic rats, nitrate alone significantly reduced plasma glucose and increased pancreatic SOD and GPx activity. Reduced plasma glucose, pancreatic MDA and NO concentrations and increased plasma insulin level and pancreatic islet insulin secretion were observed in D + Ln and DN + Ln groups. Antioxidant enzymes activities were increased in diabetic rats which received combination of nitrate and L-NAME. CONCLUSIONS: Our results showed that nitrate without effect on pancreatic islet insulin content and secretion decreased the blood glucose and slightly moderate oxidative stress and its effects in the presence of L-NAME on glucose hemostasis and pancreatic insulin secretion higher than those of nitrate alone.

Effects of platelet-rich plasma on the pancreatic islet survival and function, islet transplantation outcome and pancreatic pdx1 and insulin gene expression in streptozotocin-induced diabetic rats.

Platelet-rich plasma (PRP) is a therapeutic option in different fields based on its growth factors. We investigated influence of PRP on islet survival, function, transplantation outcomes, and pancreatic genes expression in diabetic rats. In vitro: pancreatic isolated islets were incubated with/without PRP then viability, insulin secretion, and content were assessed. In vivo: Series 1 were designed to determine whether islet treatment with PRP improves transplantation outcome in diabetic rats by evaluating plasma glucose and insulin concentrations and oxidative parameters. Series 2, effects of PRP subcutaneous injection were evaluated on pancreatic genes expression and glucose tolerance test in diabetic rats. PRP enhanced viability and secretary function of islet. Reduced glucose and malondialdehyde levels as well as increased insulin levels, superoxide dismutase activity, and expressions of pdx1 and insulin were observed in diabetic rats. PRP treatment has positive effects on islet viability, function, transplantation outcome, and pancreatic genes expression in diabetic rats.

Association Between Sex Steroids and Oxidative Status with Vitamin D Levels in Follicular Fluid of Non-obese PCOS and Healthy Women.

BACKGROUND: Human follicular fluid (FF) is rich in hormones and antioxidants. Many components of FF differ in follicles of patients with polycystic ovary syndrome (PCOS). Regarding vitamin D effects on gene expression, 25(OH)D level of FF and its association with oxidative status and sex steroids dysregulation in PCOS group was evaluated and compared to controls of Non-obese healthy women. METHODS: FF of 50 non-obese healthy women and 50 women with PCOS (18-36 years old) who were candidates for IVF/ICSI was aspirated on the oocyte retrieval day. Sex steroids and 25(OH)D levels were measured by ELISA. Reactive oxygen species (ROS) levels, total antioxidant capacity (TAC), and activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were assessed by chemiluminescence and spectrophotometric methods. Data were analyzed by unpaired t-test or Mann-Whitney test, and Pearson correlation coefficient. The p<0.05 was considered statistically significant. RESULTS: Estradiol, progesterone, 25(OH)D, TAC, and activities of SOD, GPx, and CAT in FF of women with PCOS were significantly lower, whilst their free and total testosterone and ROS levels were significantly higher than controls. There were significant positive correlations between FF levels of 25(OH)D with TAC, estradiol and progesterone concentrations, SOD, GPx, and CAT activities. Negative correlations were found between 25(OH)D with free and total testosterone, and ROS levels. CONCLUSION: Despite different hormonal and antioxidant levels in FF of normal and cystic follicles, the correlation between 25(OH)D levels with sex steroids and oxidative stress markers showed a possible role of 25(OH)D in regulating sex hormones secretion and enhancement of antioxidant defense.

Impact of Hydroalcoholic Extract of Humulus Lupulus L. on Sperm Quality, Reproductive Organs and Hormones in Male Rats.

OBJECTIVE: To investigate the impact of Humulus Lupulus L. hydroalcoholic extract on the body weights, reproductive organs, sperm quality and hormone levels in male rats. METHODS: By simple random sampling method, seventy male Sprague-Dawley rats were randomly assigned to 7 groups including control group [distilled water, 1 mL/(kg•d)], Tween 80 group [25% Tween 80 solution, 1 mL/(kg•d)], olive oil group [olive oil, 1 mL/(kg•d)], diethyl stilbestrol (DES) group [DES, 100 µg/(kg•body weight)], H50, H150 and H450 [50, 150 and 400 mg/(kg•d) of Humulus Lupulus L extract, respectively]. The administration was performed via gavage once daily for 7 weeks. Body and reproductive organs weights including testes, seminal vesicles, epididymis and prostate were weighted and epididymal sperm quality were determined by digital balance. Blood samples were collected and serum free testosterone (T), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estrogen (E2) levels were measured by rat specific enzyme-linked immunosorbent assay. RESULTS: The percentage increase in mean body weights of rats in the DES and H50, H150 and H450 groups decreased significantly compared to olive oil and Tween 80 groups (all P<0.05). The weights of seminal vesicle, epididymis and testes in rats receiving H50 were significantly higher than the control group (P<0.05 or P<0.01). The sperm count in the rats receiving H50 was significantly lower than the control group (P<0.05). The sperm motile characteristics of the rats receiving hydroalcoholic extract at and DES were significantly lower than those of the control or rats receiving vehicles (all P<0.05). In H50, H150, H450 and DES groups, T and LH levels were decreased, and E2 was significantly increased compared to the control (P<0.05 or P<0.01). The FSH level did not change in all groups (P>0.05). CONCLUSION: Humulus Lupulus L. extract significantly increased the seminal vesicle and testes weights and reduced the sperm motility.

Platelet-rich plasma improves impaired glucose hemostasis, disrupted insulin secretion, and pancreatic oxidative stress in streptozotocin-induced diabetic rat.

Our study aimed to investigate the effects of platelet-rich plasma (PRP) on impaired glucose homeostasis, disrupted islet insulin secretion, and pancreatic oxidative status in streptozotocin (STZ)-diabetic rats. A total of 64 Sprague-Dawley male were randomized to four groups including controls, diabetes, control-PRP, and diabetes-PRP. The rats received the PRP (0.5 ml/kg, SC injection) twice weekly for 4 weeks. Plasma glucose and insulin levels, pancreatic oxidative stress markers and islet insulin secretion and content were measured. Compared with the control group, in the diabetic group, increased plasma glucose and malondialdehyde (MDA) levels and decreased plasma insulin level, islet insulin secretion, pancreatic superoxide dismutase (SOD), and catalase activities were observed. PRP treatment significantly reduced plasma glucose and MDA levels and enhanced plasma insulin, antioxidant enzyme activity, islet insulin secretion, and content in the diabetic rats. These findings showed that PRP can improve pancreatic islet insulin secretion, pancreatic oxidative stress and regulate plasma insulin and glucose levels in diabetic rats.

Radiofrequency radiation emitted from Wi-Fi (2.4 GHz) causes impaired insulin secretion and increased oxidative stress in rat pancreatic islets.

PURPOSE: There is a great concern regarding the possible adverse effects of electromagnetic radiation (EMR). This study investigated the effects of EMR induced by Wi-Fi (2.45 GHz) on insulin secretion and antioxidant redox systems in the rat pancreas. MATERIALS AND METHODS: Adult male Sprague-Dawley rats in the weight range of 230-260 g were divided into control, sham, Wi-Fi exposed groups. After long-term exposure (4 h/day for 45 days) to Wi-Fi EMR, plasma levels of glucose and insulin during intraperitoneal glucose tolerance test were measured. Islet insulin secretion and content, lipid peroxidation, and antioxidant status in pancreas of rats were determined. RESULTS: Our data showed that the weight gain in the WI-FI exposed group was significantly lower than the control group (p < .05). Wi-Fi (2.45 GHz)-exposed group showed hyperglycemia. Plasma insulin level and glucose-stimulated insulin secretion from pancreatic islet were significantly reduced in the Wi-Fi-exposed group. EMR emitted from Wi-Fi caused a significant increase in lipid peroxidation and a significant decrease in GSH level, SOD, and GPx activities of the pancreas. CONCLUSIONS: These data showed that EMR of Wi-Fi leads to hyperglycemia, increased oxidative stress, and impaired insulin secretion in the rat pancreatic islets.

Induction of oxidative stress, suppression of glucose-induced insulin release, ATP production, glucokinase activity, and histomorphometric changes in pancreatic islets of hypothyroid rat.

Thyroid hormones have important role in metabolism and impairment of glucose metabolism and insulin secretion has been shown in hypothyroid rats but the exact mechanisms for this defect are poorly understood. The aim of this study was to investigate the effect of hypothyroidism on oxidative stress parameters, insulin secretory pathway and histomorphometric changes of pancreas. In the isolated islets of the control and methimazole -treated hypothyroid insulin secretion and content, ATP production, Glucokinase, and hexokinase specific activity and kATP and L-type channels sensitivity were assayed. In order to determine oxidative stress parameters, antioxidant enzymes and lipid peroxidation were measured in pancreatic homogenates. Histomorphometric changes and histochemistry of the islet in both groups were compared. Results showed that plasma glucose and insulin concentration and their area under the curve during IPGTT in hypothyroid group were respectively higher and lower than the controls. In the hypothyroid islets, glucose stimulated insulin secretion, ATP production, hexokinase and glucokinase activities were decreased. Hypothyroid induced a significant increased lipid peroxidation, and decreased the antioxidant enzyme activity. Compared with the control group, insulin antibody positivity, the total volume of the pancreas, islets, and the total number as well as the mean volume of the beta cells were also significantly decreased in the hypothyroid group. These findings indicate that oxidative stress produced under hypothyroidism could have a role in progression of pancreatic ß-cell dysfunction, reduced beta cell mass and decreased glucokinase activity, impairing glucose tolerance and insulin secretion.

Impaired glucose-stimulated insulin secretion and reduced ß-cell mass in pancreatic islets of hyperthyroid rats.

NEW FINDINGS: What is the central question of this study? Thyroid dysfunction can have a major impact on pancreatic function. The influence of hyperthyroidism on insulin secretion remains controversial, and the precise mechanism of its effect has not yet been elucidated. What is the main finding and its importance? The results of this study demonstrate that hyperthyroidism leads to impaired insulin secretion. It appears that the defect in insulin secretion in the hyperthyroid state probably reflects a summation of different alterations, including decreased sensitivity of ATP-sensitive K(+) and L-type Ca(2+) channels of the ß-cells and reduced ß-cell mass. To clarify the mechanism underlying the effect of thyroid hormone excess on pancreatic insulin secretion and abnormal glucose tolerance induced by hyperthyroidism, we investigated the effect of hyperthyroidism on the pancreatic ß-cell mass and two key components of the insulin secretory pathway, ATP-sensitive K(+) (KATP ) and L-type Ca(2+) channels. In control and levothyroxine-treated hyperthyroid rats, an intraperitoneal glucose tolerance test was performed, and the insulin secretion and content of the isolated islets were assayed. In order to determine the effect of hyperthyroidism on KATP and L-type Ca(2+) channels, isolated islets were exposed to specific pharmacological agents, including glibenclamide (KATP channel blocker), diazoxide (KATP channel opener) and nifedipine (L-type Ca(2+) channel blocker). Histomorphometric changes and histochemistry of the islet in both groups were compared. Our data indicated that plasma glucose and insulin concentrations during the intraperitoneal glucose tolerance test in the hyperthyroid group were, respectively, higher and lower than in the control group. Insulin secretion and content of the hyperthyroid islets were reduced. The response of hyperthyroid islets to glibenclamide, diazoxide and nifedipine and the percentage change in insulin secretion were lower than those of the control islets. Despite the increase in weight and total volume of the pancreas, the volume of the islets and the total number of insulin-positive cells in hyperthyroid rats were reduced. Our data indicated that reduced insulin secretion in the hyperthyroid group might arise from reduced ß-cell mass and an abnormality in some parts of the insulin secretory pathway, including KATP and L-type Ca(2+) channel function.

The possible mechanisms by which maternal hypothyroidism impairs insulin secretion in adult male offspring in rats.

Previous studies have recently shown that maternal hypothyroidism leads to impaired glucose metabolism and reduced insulin secretion in adult offspring in rats. The aim of this study was to locate the defect in the insulin secretion pathway induced by maternal hypothyroidism. Pregnant Wistar rats were divided into two groups; the control group consumed water, while the hypothyroid (FH) group received water containing 0.025% 6-propyl-2-thiouracil during gestation. An intravenous glucose tolerance test was carried out on 5-month-old male offspring. In in vitro studies, the effects of various secretagogues and inhibitors acting at different levels of the insulin secretion cascade were investigated, and insulin content, insulin secretion and glucokinase activity of the islets were compared. Although insulin content of the FH islets did not differ from that of control islets, insulin secretion from FH islets was reduced when it was challenged by glucose or arginine. Compared with control islets, activities of both hexokinase and glucokinase were also significantly decreased in the FH islets. Although, in both groups, increasing glibenclamide and nifedipine concentrations in the presence of 16.7 mmol l(-1) glucose increased and decreased insulin secretion, respectively, the percentage of changes in secretion of FH islets was significantly lower compared with control islets. The response of FH islets to high extracellular potassium concentration and diazoxide was also significantly lower than that of the control islets. These findings demonstrate that impaired insulin secretion in the FH group is probably related to alterations in different steps of the insulin secretion pathway and not in the insulin pool of ß-cells.

Comparison of the effect of maternal hypothyroidism on carbohydrate metabolism in young and aged male offspring in rats.

OBJECTIVE: Since thyroid hormones play fundamental roles in somatic growth and metabolism, disturbances of thyroid function affect many organs and systems. Both fetal hypothyroidism and aging can affect carbohydrate metabolism during adult life. This study aims to assess the glucose tolerance and insulin secretion capacity of islets in young and aged male offspring of mothers who were hypothyroid during pregnancy. MATERIALS AND METHODS: Pregnant Wistar rats were divided into two groups; the control group consumed water, while the hypothyroid group received water containing 0.02% of 6-propyl-2-thiouracil (200 ppm) during gestation. After birth, survival and weight of pups from both groups were followed. The intravenous glucose tolerance test (IVGTT, 0.5 g/kg glucose) was carried out in young and aged male offspring (at 3- and 12-months-old). RESULTS: In old, but not in young rats, serum glucose and insulin levels were respectively significantly higher and lower between 5 and 20 min in the fetal hypothyroid (FH) group, compared with the controls (C). Insulin secretion of the isolated islets stimulated with 5.6, 8.3, and 16 mmol/L glucose in the old FH group (240.5 ± 22.0, 457.0 ± 40.1, and 768.0 ± 57.1 respectively) were significantly lower (p = 0.014, p = 0.029 and p = 0.003 respectively), compared to the C group (327.9 ± 25.9, 579.2 ± 36.3, and 1024.0 ± 59.5 pmol/islet/min respectively). CONCLUSION: Results show that maternal hypothyroidism leads to glucose intolerance and reduced insulin secretion capacity, more obvious in older offspring. Hence it can be concluded that the effect of fetal hypothyroidism on carbohydrate metabolism may contribute to increased risk of type II diabetes in aged animals.

The effect of consuming oxidized oil supplemented with fiber on lipid profiles in rat model.

BACKGROUND: This study was conducted to evaluate the effects of consuming thermally oxidized oil supplemented with pectin on liver glutathione peroxidase activity, serum malondialdehyde and lipid profiles in male Sprague-Dawley rats. METHODS: Fifty growing male Sprague-Dawley rats were randomly divided into different groups. The diets differed only in their fat and pectin content. The diets had fresh sunflower oil or thermally oxidized sunflower oil. The diets were supplemented with pectin in the amount of 50 g/kg diet or not supplemented. Thus, there were four experimental groups: "fresh oil", "oxidized oil", "fresh oil + pectin", "oxidized oil + pectin". Study duration was 42 days. Non parametric, Kruskal-Wallis and Mann-Whitney tests were used to evaluate mean values of variables in groups. RESULTS: In oil consumption, peroxide, p- Anisidine, thiobarbituric acid, free fatty acid values and total polar compounds increased but iodine value was decreased. In the oxidized oil group compared to the fresh oil group, total cholesterol, high density lipoprotein cholesterol and malondialdehyde increased (p < 0.05). Serum malondialdehyde was decreased in the "oxidized oil + pectin" group compared to the oxidized oil alone (2.82 ± 0.51 vs. 3.61 ± 0.72 nmol/ml; p < 0.05). Total cholesterol decreased in both groups containing pectin compared to their respective diets without supplementation (70.10 ± 10.75 vs. 81.20 ± 13.10 mg/dl; p < 0.05). CONCLUSIONS: Pectin consumption could decrease serum malondialdehyde and cholesterol in the diet that contains oxidized oil. Pectin supplementation could decrease the detrimental effects of thermally oxidized oil.