Experimental Models Of Diabetes Research Articles

Evaluation of anti-diabetic potential of Ficus arnottiana Miq. leaves against in-vivo and in-vitro experimental models of diabetes

Evaluation of anti-diabetic potential of Ficus arnottiana Miq. leaves against in-vivo and in-vitro experimental models of diabetes

1-Deoxynojirimycin Mitigates Glycogen and Carbohydrate Metabolic Enzyme Alterations in High Glucose-Induced Diabetic Tilapia: Implications for Therapeutic Intervention

This study investigated the effects of 1- deoxynojirimycin (DNJ) on blood glucose levels, body weight changes, glycogen levels, and carbohydrate marker enzyme activity in a high glucose-induced experimental diabetic tilapia model. We utilized spectrophotometry assay methods to achieve this objective. DNJ treatment significantly reduced blood glucose and mitigated body weight loss compared to the diabetic control group. Furthermore, DNJ treatment increased glycogen levels in liver and muscle tissues, suggesting its potential to enhance glycogen synthesis or reduce glycogen breakdown. DNJ treatment also modulated the activity of carbohydrate marker enzymes, indicating its possible inhibitory effect on enzymes involved in carbohydrate absorption and breakdown, which in turn may improve glucose homeostasis and control. The results of this study highlight DNJ's potential as a therapeutic agent for diseases associated with glycogen metabolism and glucose homeostasis, as well as its ability to influence body weight changes in diabetic conditions. Our findings contribute to the growing body of research on DNJ as a potential therapeutic agent for illnesses linked to glycogen and underscore its therapeutic potential for future treatments targeting glucose metabolism, glycemic control, and weight management.

Dapagliflozin Mitigated Elevated Disomic and Diploid Sperm in a Mouse Model of Diabetes and Recover the Disrupted Ogg1, Parp1, and P53 Gene Expression.

Increases in numerical chromosomal syndromes were observed in children of diabetic mothers. However, the effects of diabetes on male reproduction, specifically numerical chromosomal aberrations (aneuploidy), have not been studied. Furthermore, despite the increasing use of dapagliflozin for diabetes treatment, no data exists on its ability to affect aneuploidy levels in germ cells. Thus, our investigation aimed to evaluate the effects of diabetes on spontaneous sperm aneuploidy and whether treatment with dapagliflozin influences the frequency of aneuploidy in the sperm of an experimental diabetic animal model. Our findings show that dapagliflozin has no aneugenic effects on the meiotic stages of spermatogenesis. In contrast, diabetes raised the frequency of aneuploidy, and dapagliflozin administration decreased the elevated levels of disomic and diploid sperm. The level of oxidative stress was markedly increased in diabetic mice, but were reduced by dapagliflozin treatment. Furthermore, the expression of some of DNA repair genes was disrupted in diabetic animals, whereas dapagliflozin therapy restored these disruptions and significantly enhanced DNA repair. Thus, dapagliflozin may effectively ameliorate diabetes-induced aneugenic effects on male meiosis and treating diabetic patients with dapagliflozin may effectively mitigate the transmission of diabetes-induced chromosomal defects to offspring.

Experimental diabetic animal models to study diabetes and diabetic complications

Diabetes is an endocrine illness involving numerous physiological systems. To understand the intricated pathophysiology and disease progression in diabetes, small animals are still the most relevant model systems, despite the availability and progression in numerous invitro and insilico research methods in recent years. In general, experimental diabetes is instigated mainly due to the effectiveness of animal models in illuminating disease etiology. Most diabetes trials are conducted on rodents, while some research is conducted on larger animals. This review will discuss the methodology and mechanisms in detail for preparing diabetic animal models, considering the following important points. The exact pathophysiology of the disease may or may not be replicated in animal models, the correct induction doses must be given and the combination of different approaches for the models is recommended to get desired results.•Animal models are essential to understand diabetes etiology and pathophysiology.•Diabetic models can be developed in both rodents and non-rodents.•Chemically induced and genetic models of diabetes are widely used to study diabetes and diabetic complications.

Evaluation of the effects of ghrelin and metformin on sperm parameters, testosterone hormones, and immunohistochemical and immunofluorescent markers in an experimental diabetes model

Evaluation of the effects of ghrelin and metformin on sperm parameters, testosterone hormones, and immunohistochemical and immunofluorescent markers in an experimental diabetes model

Clinical and laboratory assessment of hormonal and metabolic disorders in experimental animals with alloxan, streptozotocin and dithizone diabetes

The basic place in experimental diabetology is engaged by chemical models of diabetes. In these patterns, β-cells in pancreatic islet tissue are selectively targeted by diverse agents. Pathogenetic mechanisms of hormonal and metabolic disorders in animals were studied on models of alloxan, streptozotocin and dithizone diabetes. The experiment was carried out on male Wistar rats. Three models of experimental diabetes were created. The groups were equal in terms of observation time (6, 12, 24 months) and number. A complex of laboratory-biochemical methods of lipid and protein metabolism was consumed. Serum enzymes were also determined. The level of glycemia in the studied animals after the introduction of alloxan and streptozotocin ranged from 13.4 to 18.6 mmol/l, glucosuria, polydipsia, polyphagia were observed. A significant (p<0.01) increase in glycemia by 3.10 times, glycated hemoglobin - by 3.16 times, a decrease (p<0.01) of IRI - by 3.76 times and C-peptide - by 2.05 times in animals with streptozotocin diabetes compared with intact animals. Serious lipid metabolism disorders were discovered in alloxan, streptozotocin, and especially dithizone diabetes (24 months of follow-up). This was manifested in a significant (p<0.01) increase in the level of triglycerides - by 1.66 times, atherogenic index (p<0.01) - by 4.43 times and a decrease (p<0.05) in the level of HDL - by 1 43 times compared with the intact CI3 group, as well as an increase in FFA, TCH, LDL, VLDL. In animals with alloxan and dithizone diabetes, the functional activity of the pituitary gland was lessened (the level of growth hormone and CTH (p<0.01), the adrenal cortex and pancreatic α-cells (p<0.01), the activity of the sympathoadrenal system was enlarged, which was reaffirmed by a significant (p<0.01) by an increase in the level of adrenaline, noradrenaline - by 1.42 times. An above pronounced suppression of the endocrine glands was observed in animals with streptozotocin diabetes.

Histopathological evaluation of the effects of sildenafil on organ damage in a diabetic rat model

Aims: In this study, it was aimed to show the effects of sildenafil on heart, liver and kidney tissues histopathologically by creating an experimental diabetes model with streptozocin.
 Methods: Male adult Sprague dawley rat (48) was used in the study. The rats were first divided into three groups as control group, the diabetes group and the diabetes+sildenafil group. Each group was divided into two groups within itself. Streptozotocin 40 mg/kg was administered intraperitoneally to the rats in the groups that would develop diabetes and diabetes+sildenafil diabetes. Rats with blood glucose levels of 250 mg/dl and above after 48 hours were considered diabetic. Sildenafil citrate 10mg/kg/day was given by gavage to the diabetes+sildenafil group. At the end of the experiment heart, liver and kidney tissues were placed in formaldehyde solution. Hematoxylin-Eosin staining was applied to the sections taken. Histological changes in the stained sections were evaluated by a histologist. Histological evaluation was performed semi-quantitatively in heart, liver and kidney tissue. In the assessment, the findings of the tissues were scored and statistical analysis was performed.
 Results: Histological findings of heart, liver and kidney tissues were examined. It was determined that less organ damage was seen in the diabetes+sildenafil group compared to the Diabetes group.
 Conclusion: In our study, it has been demonstrated histologically that sildenafil can be a drug that has an antioxidant effect in tissue by helping to protect cell structure and architecture against heart, liver and kidney tissue damage caused by diabetes. It should not be overlooked that it is important to determine the appropriate dose and frequency of use of sildenafil in revealing these effects.

A mutual regulatory loop between miR-155 and SOCS1 influences renal inflammation and diabetic kidney disease

Diabetic kidney disease (DKD) is a common microvascular complication of diabetes, a global health issue. Hyperglycemia, in concert with cytokines, activates the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway to induce inflammation and oxidative stress contributing to renal damage. There is evidence of microRNA-155 (miR-155) involvement in diabetes complications, but the underlying mechanisms are unclear. In this study, gain- and loss-of-function experiments were conducted to investigate the interplay between miR-155-5p and suppressor of cytokine signaling 1 (SOCS1) in the regulation of the JAK/STAT pathway during renal inflammation and DKD. In experimental models of mesangial injury and diabetes, miR-155-5p expression correlated inversely with SOCS1 and positively with albuminuria and expression levels of cytokines and prooxidant genes. In renal cells, miR-155-5p mimic downregulated SOCS1 and promoted STAT1/3 activation, cytokine expression, and cell proliferation and migration. Conversely, both miR-155-5p antagonism and SOCS1 overexpression protected cells from inflammation and hyperglycemia damage. Invivo, SOCS1 gene delivery decreased miR-155-5p and kidney injury in diabetic mice. Moreover, therapeutic inhibition of miR-155-5p suppressed STAT1/3 activation and alleviated albuminuria, mesangial damage, and renal expression of inflammatory and fibrotic genes. In conclusion, modulation of the miR-155/SOCS1 axis protects kidneys against diabetic damage, thus highlighting its potential as therapeutic target for DKD.

The Effect of Lavandula stoechas on Wound Healing in an Experimental Diabetes Model.

Diabetic foot is a consequential and dangerous complication of diabetes, contributing to decreased quality of life, escalated hospitalizations, and increased mortality rates. Using an experimental model of diabetes, this study aims to investigate the effect of Lavandula stoechas on wound healing. A total of 35 albino Wistar rats, 250-350 grams in weight, were used. The rats were divided into five groups, seven rats in each group. Of these, 21 rats were induced with 50 mg/kg streptozotocin (STZ) to mimic the diabetic condition. Additionally, 14 rats remained non-diabetic and served as the control group. The diabetic rats were further divided into three subgroups. The non-diabetic group was split into two subgroups based on the dressing materials used (allicin, physiological serum, and control). Wound dimensions were assessed on Days 0, 7, 14, and 21. Biopsies were taken from the wound sites at the same time. There were significant differences between groups on Days 7, 14, and 21. The percentage of healing was highest in the Lavandula Stoechas group on Days 7, 14, and 21. Microscopic examination of the biopsies supported accelerated wound healing on Days 7 and 14. Reduced mononuclear cell density and increased hair follicle and adipose tissue development were observed in the DM (diabetes mellitus)-Lavandula Stoechas group on Day 7. On Day 14, the DM-Lavandula Stoechas group increased collagen levels and hair follicles. Similarly, the non-DM-Lavandula Stoechas group showed reduced bullae, dermal edema, and intraepithelial edema on Day 7. This was followed by increased fibroblast levels on Day 14. In conclusion, this study provides compelling evidence for the potential of Lavandula stoechas extract in the enhancement of diabetic wound healing. The multiple interactions revealed here highlight the need for further investigation into the underlying mechanisms. A cost-effective use of Lavandula stoechas opens up promising prospects in managing diabetic foot healing. This warrants additional research and clinical translation.

Therapy for CKD and DKD

Diabetic kidney disease is a major cause of renal failure that urgently necessitates a breakthrough in disease management. Specific remedies are needed for preventing Type 2 diabetes which causes significant changes in an array of plasma metabolites. By untargeted metabolome analysis, phenyl sulfate (PS) increased with the progression of diabetes. In experimental diabetes models, PS administration induces albuminuria and podocyte damage due to the mitochondrial dysfunction. By clinical diabetic kidney disease (DKD) cohort analysis, it was also confirmed that the PS levels significantly correlate with basal and predicted 2-year progression of albuminuria. Phenol is synthesized from dietary tyrosine by gut bacterial-specific tyrosine phenol-lyase (TPL), and absorbed phenol is metabolized into PS in the liver. Inhibition of TPL reduces not only the circulating PS level but also albuminuria in diabetic mice. TPL inhibitor did not significantly alter the major composition, showing the non-lethal inhibition of microbial-specific enzymes has a therapeutic advantage, with lower selective pressure for the development of drug resistance. Clinically, 362 patients in a multi-center clinical study in diabetic nephropathy cohort (U-CARE) were analyzed with full data. The basal plasma PS level significantly correlated with ACR, eGFR, age, duration, HbA1c and uric acid, but not with suPAR. Multiple regression analysis revealed that ACR was the only factor that significantly correlated with PS. By stratified logistic regression analysis, in the microalbuminuria group, PS was the only factor related to the amount of change in the 2-year ACR in all models. PS is not only an early diagnosis marker, but also a modifiable cause and therefore a target for the treatment of DKD. Reduction of microbiota-derived phenol by the inhibitor should represent another aspect for developing drugs of DKD prevention.

The Effects of Regular Treadmill Exercise on Some Blood Parameters in Diabetes Mellitus

This study aims to determine the effects of regular treadmill exercise on some blood parameters in rats with an experimental diabetes model. In the study, 36 Wistar Albino rats were divided into four groups Control (C), Exercise (E), Diabetes (D), and Diabetes+Exercise (DE). A single dose of 60 mg/kg STZ solution was injected intraperitoneally (i.p) into the D and DE groups to create a diabetes model. After diabetes induction, E and DE groups were given running exercises at 20 m/min and 45 minutes daily for four weeks. According to the data obtained, while lipid profile (TC, LDL, TG) and liver enzyme (ALT, AST) levels increased significantly in group D compared to group C, HDL and TP levels were found to decrease. However, a decrease was observed in parameters other than HDL and TP in the DE group. It was also observed that the mineral and vitamin (Vit D, Ca, Mg, and Zn) levels decreased in the D group compared to the C group, while these values tended to increase in the DE group. As a result, the experiment shows that a four week regular exercise program in rats with diabetes has a therapeutic, preventive, and protective effect on lipoprotein levels, liver enzyme markers, and micronutrient levels.

Corrigendum to: Betaine ameliorates high glucose-induced oxidative stress in granulosa cells.

In diabetes, abnormalities of granulosa cells (GCs) and steroidogenesis are associated with hyperglycaemia-induced oxidative stress. Betaine has beneficial effect in experimental model of diabetes by reducing oxidative stress, inflammation, and apoptosis. In this study we investigate the effects of betaine to prevent oxidative stress in GCs induced by high glucose and improve steroidogenesis. Primary GCs, isolated from ovarian follicles of C57BL/6 mice were cultured in 5mM (control) and 30mM (hyperglycaemia) of glucose and in presence of 5mM of betaine for 24h. Then antioxidant enzymes, malondialdehyde, oestradiol and progesterone were measured. In addition, the expression of Nrf2 and NF-κB , antioxidant enzymes (Sod1 , Gpx and Cat ) were analysed by qRT-PCR assay. We observed significant (P NF-κB and down-regulation of Nrf2 due to high concentration of glucose. Also significant (P Cat , Sod1 and GPx ) and activity reduction of these enzymes as well as significant (P NF-κB and up-regulating the expression of Nrf2 , Cat , Sod1 and GPx . It was also shown that betaine in the presence of FSH significantly (P Conclusion: Betaine compensated the antioxidant stress in mouse GCs under hyperglycaemic condition via regulation of Nrf2/NF-κB at transcription level. As betaine is a natural product and no side effect has been reported to today, we suggest more research needs to be carried out especially on patients whom suffer from diabetes to find the probability of using betaine as a therapeutic agent.

Pax4 in Health and Diabetes

Paired box 4 (Pax4) is a key transcription factor involved in the embryonic development of the pancreatic islets of Langerhans. Consisting of a conserved paired box domain and a homeodomain, this transcription factor plays an essential role in early endocrine progenitor cells, where it is necessary for cell-fate commitment towards the insulin-secreting β cell lineage. Knockout of Pax4 in animal models leads to the absence of β cells, which is accompanied by a significant increase in glucagon-producing α cells, and typically results in lethality within days after birth. Mutations in Pax4 that cause an impaired Pax4 function are associated with diabetes pathogenesis in humans. In adulthood, Pax4 expression is limited to a distinct subset of β cells that possess the ability to proliferate in response to heightened metabolic needs. Upregulation of Pax4 expression is known to promote β cell survival and proliferation. Additionally, ectopic expression of Pax4 in pancreatic islet α cells or δ cells has been found to generate functional β-like cells that can improve blood glucose regulation in experimental diabetes models. Therefore, Pax4 represents a promising therapeutic target for the protection and regeneration of β cells in the treatment of diabetes. The purpose of this review is to provide a thorough and up-to-date overview of the role of Pax4 in pancreatic β cells and its potential as a therapeutic target for diabetes.

Inhibition of Ferroptosis in the Subacute Phase of Ischemic Stroke Worsens Aversive Learning In Diabetic Rats: A Randomized Double-Blind Preclinical Trial

Diabetes increases the risk of hemorrhagic transformation as well as post-stroke cognitive impairment (PCSI). We have shown that iron chelation in the subacute phase improves stroke cognitive outcomes in experimental models of diabetes. We hypothesized that inhibition of ferroptosis, iron-induced cell death, in the post-stroke period will prevent PSCI in diabetic animals. Methods: Male rats, housed in reverse light cycle, underwent sham or 60-min middle cerebral artery occlusion surgery 8 weeks after diabetes onset. After MRI, rats that met the preset inclusion criteria (adhesive removal time > 35 sec. and either a modified Bederson score <= 6 or weight loss > 10% on Day 3) were randomized to ferroptosis inhibitor UAMC-3 (2mg/kg) or vehicle treatment for 2 weeks (n=8-12). Sensorimotor and cognitive outcomes were monitored for 8 weeks in the dark (active) cycle. Results: As confirmed by MRI, inclusion criteria predicted successful stroke surgery in 95% of the animals. There were significant acute neurological deficits. Long-term weight gain and survival were better in this cohort as compared to our historical data collected in regular light cycle experiments. Blood glucose levels were comparable. In contrast to our previous data, there were no significant differences in indices measured by novel object recognition (NOR), Y-maze, and sucrose preference tests after stroke but there was a trend for a greater number of animals showing a cognitive decline in treated cohorts. Step-through latency in the passive avoidance test (PAT) was lower in the treated stroke group. Open field (OF) suggested anxiety-like behavior in RX group. Conclusions: Preset inclusion criteria were effective in controlling for stroke severity. Ferroptosis inhibition impaired aversive learning and appeared to worsen cognitive outcomes in some of the animals. Better post-stroke weight gain/maintenance and greater engagement of animals in behavioral tests conducted in the “dark” cycle may explain the lack of a progressive memory decline after stroke. While further studies are required to better understand whether ferroptosis and housing lighting impacts stroke recovery in diabetes, based on current findings, inhibition of ferroptosis with UAMC-3 is not desirable. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Insulin Sensitization by PPARγ and GLUT-4 Overexpression/Translocation Mediates the Antidiabetic Effect of Plantago australis.

Plantago australis Lam. Subsp. hirtella (Kunth) Rahn is a medicinal plant used as a diuretic, anti-inflammatory, antibacterial, throat cancer treatment and for the control of diabetes. P. australis was collected in the state of Morelos, México. The hydroalcoholic extract (HAEPa) of P. australis was obtained by maceration and concentrated in vacuo. Once dry, it was evaluated through an oral glucose tolerance test (OGTT) in normoglycemic mice and in a non-insulin-dependent diabetic mice model. The expression of PPARγ and GLUT-4 mRNA was determined by rt-PCR, and GLUT-4 translocation was confirmed by confocal microscopy. The toxicological studies were conducted in accordance with the guidelines suggested by the OECD, sections 423 and 407, with some modifications. HAEPa significantly decreased glycemia in OGTT curves, as well as in the experimental diabetes model compared to the vehicle group. In vitro tests showed that HAEPa induced an α-glucosidase inhibition and increased PPARγ and GLUT-4 expression in cell culture. The LD50 of HAEPa was greater than 2000 mg/kg, and sub-chronic toxicity studies revealed that 100 mg/kg/day for 28 days did not generate toxicity. Finally, LC-MS analysis led to the identification of verbascoside, caffeic acid and geniposidic acid, and phytochemical approaches allowed for the isolation of ursolic acid, which showed significant PPARγ overexpression and augmented GLUT-4 translocation. In conclusion, HAEPa induced significant antidiabetic action by insulin sensitization through PPARγ/GLUT-4 overexpression.

Blood-Glucose-Powered Metabolic Fuel Cell for Self-Sufficient Bioelectronics.

Currently available bioelectronic devices consume too much power to be continuously operated on rechargeable batteries, and are often powered wirelessly, with attendant issues regarding reliability, convenience, and mobility. Thus, the availability of a robust, self-sufficient, implantable electrical power generator that works under physiological conditions would be transformative for many applications, from driving bioelectronic implants and prostheses to programing cellular behavior and patients' metabolism. Here, capitalizing on a new copper-containing, conductively tuned 3D carbon nanotube composite, an implantable blood-glucose-powered metabolic fuel cell is designed that continuously monitors blood-glucose levels, converts excess glucose into electrical power during hyperglycemia, and produces sufficient energy (0.7mW cm-2 , 0.9V, 50mm glucose) to drive opto- and electro-genetic regulation of vesicular insulin release from engineered beta cells. It is shown that this integration of blood-glucose monitoring with elimination of excessive blood glucose by combined electro-metabolic conversion and insulin-release-mediated cellular consumption enables the metabolic fuel cell to restore blood-glucose homeostasis in an automatic, self-sufficient, and closed-loop manner in an experimental model of type-1 diabetes.

Wound Healing Activity of Cotton Fabrics Loaded with Silver Nanoparticles in Experimental Model of Diabetes

Diabetes is connected with diminished wound healing, that makes patients liable to continuing difficult wounds. Metal nanomaterials as single conjugates have established to keep possible properties of wound when metal nanoparticles are coupled with other wound covering materials. This study aimed to investigate a possible role of cotton fabrics full with silver nanoparticles (AgNPs) to enhance wound healing in diabetic model induced by streptozotocin (STZ).Animals were classified into four groups including the wounded group that were equivalently covered with sterile dressing that made of cotton fabric which had been saturated with different concentrations of silver nanoparticles, and the control group that was preserved with only cotton covering without any treatment (blank group); percent of wound contraction in different studied groups was estimated. Plasma nitric oxide (NO), malodialdehyde (MDA), reduced glutathione (GSH) were measured. Serum neutrophil elastase and nuclear factor kappa b (NF-κb) were assayed by ELISA. Homocystiene (Hcy) was estimated by HPLC. Our results revealed an elevation in wound area, MDA, NF-κb, Hcy, and elastase in the wound group compared to treated groups concomitant with a decrease in plasma nitric oxide and reduced glutathione activities, while treatment with AgNPs significantly ameliorated these parameters in treated group compared to blank group. AgNPs showed high wound contraction rates according to their used concentration .In conclusion; AgNPs have gained considerable attention amongst researchers in wound healing applications, owing to their physicochemical and biological properties. AgNPs promote wound healing and effectively control the growth of microorganisms at the wound site, and this strategy plays an important role in the treatment of wounds.

Effect of silymarin on the parameters of oxidative stress in hearts in the course of diabetes mellitus in Wistar rats

Chronic hyperglycemia is one of the most important causes of the formation of oxygen free radicals in diabetes, which damage various organs. Damage to proteins and lipids in the heart can lead to the development of diabetic cardiomyopathy, which in turn may cause cardiovascular failure. In order to counteract oxidative stress, the innate antioxidant mechanisms of the system should be supported by supplementation with exogenous antioxidants, for instance of plant origin. In this experiment, the role of silymarin, a plant-derived flavonolignan on the oxidative stress parameters and oxidative damage markers in the hearts was determined in an experimental model of diabetes. Male Wistar rats were injected with streptozotocin at a dose of 60 mg/kg (ip). Then, silymarin was administered at doses of 50 and 100 mg/kg for four weeks via a gastric tube. In diabetic animals an increase in malondialdehyde, advanced oxidation protein products, as well as increased activity of antioxidant enzymes in heart tissues was noted. Administration of silymarin inhibited oxidative stress by increasing the total antioxidant response, decreasing the concentration of malondialdehyde and advanced oxidation protein products and a slight increase in the level of glutathione. It can be concluded that the redox state in the examined tissue improved. Based on the results in can be concluded that silymarin demonstrates a potential in preventing the development of oxidative damage in the heart tissue in the course of experimental diabetes.

Umbilical cord mesenchymal stromal cells transplantation delays the onset of hyperglycemia in the RIP-B7.1 mouse model of experimental autoimmune diabetes through multiple immunosuppressive and anti-inflammatory responses.

Type 1 diabetes mellitus (T1DM) is an autoimmune disorder specifically targeting pancreatic islet beta cells. Despite many efforts focused on identifying new therapies able to counteract this autoimmune attack and/or stimulate beta cells regeneration, TD1M remains without effective clinical treatments providing no clear advantages over the conventional treatment with insulin. We previously postulated that both the inflammatory and immune responses and beta cell survival/regeneration must be simultaneously targeted to blunt the progression of disease. Umbilical cord-derived mesenchymal stromal cells (UC-MSC) exhibit anti-inflammatory, trophic, immunomodulatory and regenerative properties and have shown some beneficial yet controversial effects in clinical trials for T1DM. In order to clarify conflicting results, we herein dissected the cellular and molecular events derived from UC-MSC intraperitoneal administration (i.p.) in the RIP-B7.1 mouse model of experimental autoimmune diabetes. Intraperitoneal (i.p.) transplantation of heterologous mouse UC-MSC delayed the onset of diabetes in RIP-B7.1 mice. Importantly, UC-MSC i. p. transplantation led to a strong peritoneal recruitment of myeloid-derived suppressor cells (MDSC) followed by multiple T-, B- and myeloid cells immunosuppressive responses in peritoneal fluid cells, spleen, pancreatic lymph nodes and the pancreas, which displayed significantly reduced insulitis and pancreatic infiltration of T and B Cells and pro-inflammatory macrophages. Altogether, these results suggest that UC-MSC i. p. transplantation can block or delay the development of hyperglycemia through suppression of inflammation and the immune attack.

Effects of RF and ELF Radiation on Oxidative Stress of Brain Tissue and Plasma of Diabetic Rats

Objective: Exposure to Radio Frequency (RF) and Extremely Low Frequency (ELF) radiation is increasing steadily with the progress of technology and industrialization. The aim of this study was to investigate whether RF and ELF radiation are oxidative stress effects in the plasma and brain tissue of diabetic and non-diabetic rats. Methods: Experiment groups were designed as follows; C (control), S (sham), ELF (ELF radiation exposure), RF (RF radiation exposure), ELF+RF (ELF and RF radiation exposure), D-C (Diabetic Control), D-S (Diabetic Sham), D-ELF (Diabetic ELF), D-RF (Diabetic RF), D-ELF+RF (Diabetic ELF+RF). The experimental diabetes model was induced with a single dose of 65mg/kg streptozotocin (STZ). 2100 MHz RF and 50 Hz ELF radiation groups exposed for 1 month. Total nitric oxide (NOx), malondialdehyde (MDA) and total sulfhydryl groups (RSH) / glutathione (GSH) levels were measured in plasma and brain tissue. Results: RF + ELF radiation exposure caused an increase in NOx and MDA levels in plasma and brain tissue of diabetic and non-diabetic rats (p<0.05). Exposure to RF and RF + ELF radiation caused a decrease in plasma RSH / tissue GSH levels in non-diabetic rats (p<0.05). Conclusion: The most prominent effect was seen in the diabetic group with RF + ELF radiation exposure.