Induced Diabetes In Mice Research Articles

EFFECT OF ALOE VERA AND CINNAMOMUM TAMALA ON BODY WEIGHT AND FEED INTAKE OF INDUCED DIABETIC MICE

Intraperitoneal injection of alloxanmonohydrate (200mg/kg)was used to inducediabetes in mice, with blood glucose levels(fasting) morethan 150mg/dl. Sixty nine mice were dividedinto 4 groups, Group I was non diabetic (normal). Group II was diabetic, Group III was the diabeticand treated with Cinnamomumtamala and group IV was diabetic and Aloe vera treated. There was noincrease in the blood glucoseat random and fasting in group Iwhereas, group II showed an increase inblood sugar level (91.00±2.65mg/dl to 250.00±3.79mg/dl) post 21 days. Cinnamomumtamala(50mg/kg) and Aloe vera (400mg/kg) appeared effective in reducing the blood sugar levels after 21days treatment. There was an increase in intake of feed and drop in body weight of group II comparedto group I. Cinnamomumtamala (50mg/kg) and Aloe vera (400mg/kg) was found effective regardingdecrease in feed intake. Increase in weight of mice occurred treated with Cinnamomumtamala(50mg/kg) and Aloe vera (400mg/kg)as compared to diabetic mice. Cinnamomumtamala and Aloevera were potentially efficient to treat hyperglycemia at recommended oral doses of 50 mg/kg and400mg/kg of body weight respectively.

An Investigation of The Effect of Extracellular Vesicles Isolated from Mouse Embryonic Fibroblasts on Wound Healing in an Experimental Diabetic Mouse Model.

This study aimed to investigate the effects of Extracellular Vesicles (EV) secreted from mouse embryonic fibroblasts EV on wound healing of full-thickness skin defect in a diabetic mouse model. The study included both in vitro and in vivo experimental studies 82 mice. In the in vitro stage of the experimental study, hysterectomy was performed on two mice between the 13-14th days of pregnancy and then EV was isolated by cell culturing. VEGF, IL-6, and TNF-α biomarkers were examined in tissue homogenate. Moreover, tissue taken from wound area was also subjected to histopathologic scoring. EV augmented the effect of VEGF. Therefore promoted angiogenesis increases the transport of cells, essential oxygen and nutrients in the wound area. Extracellular vesicles isolated from mouse embryonic fibroblasts have been found to accelerate wound healing in diabetes. The findings obtained from this experimental study indicate that EV isolated from mouse embryonic fibroblasts accelerate the wound healing process in experimentally induced-diabetes in mice.

Silk derived formulations for accelerated wound healing in diabetic mice.

BackgroundThe present study aimed to prepare effective silk derived formulations in combination with plant extract (Aloe vera gel) to speed up the wound healing process in diabetic mice.MethodsDiabetes was induced in albino mice by using alloxan monohydrate. After successful induction of diabetes in mice, excision wounds were created via biopsy puncture (6 mm). Wound healing effect of silk sericin (5%) and silk fibroin (5%) individually and in combination with 5% Aloe vera gel was evaluated by determining the percent wound contraction, healing time and histological analysis.ResultsThe results indicated that the best biocompatible silk combination was of 5% silk fibroin and 5% Aloe vera gel in which wounds were healed in 13 days with wound contraction: 98.33 ± 0.80%. In contrast, the wound of the control group (polyfax) healed in 19 day shaving 98.5 ± 0.67% contraction. Histological analysis revealed that the wounds which were treated with silk formulations exhibited an increased growth of blood vessels, collagen fibers, and much reduced inflammation.ConclusionIt can be concluded that a combination of Bombyx mori silk and Aloe vera gel is a natural biomaterial that can be utilized in wound dressings and to prepare more innovative silk based formulations for speedy recovery of chronic wounds.

Successful induction of diabetes in mice demonstrates no gender difference in development of early diabetic retinopathy.

PurposeFemale mice have been found to be resistant to streptozotocin (STZ)-induced diabetes, and pre-clinical research related to diabetic complications commonly omits females. The purpose of this study was to develop a method to induce diabetes in female mice, and to determine if retinas of diabetic female mice develop molecular changes and histopathological abnormalities comparable to those which develop in male diabetic mice.MethodsTo induce diabetes, animals of both sexes received daily intraperitoneal (i.p.) injection of STZ for 5 consecutive days at 55 mg/kg BW (a dose that is known to induce diabetes in male mice) or for females, 75 mg/kg BW of STZ. Retinal abnormalities that have been implicated in the development of the retinopathy (superoxide generation and expression of inflammatory proteins, iNOS and ICAM-1) were evaluated at 2 months of diabetes, and retinal capillary degeneration was evaluated at 8 months of diabetes.ResultsDaily i.p. injection of STZ for 5 consecutive days at a concentration of 55 mg/kg BW was sufficient to induce diabetes in 100% of male mice, but only 33% of female mice. However, females did become hyperglycemic when the dose of STZ administered was increased to 75 mg/kg BW. The resulting STZ-induced hyperglycemia in female and male mice was sustained for at least 8 months. After induction of the diabetes, both sexes responded similarly with respect to the oxidative stress, expression of iNOS, and degeneration of retinal capillaries, but differed in the limited population evaluated with respect to expression of ICAM-1.ConclusionsThe resistance of female mice to STZ-induced diabetes can be overcome by increasing the dose of STZ used. Female mice can, and should, be included in pre-clinical studies of diabetes and its complications.

Antidiabetic Activity of Chemically Synthetic Compound on Alloxan Induced Diabetes in Mice

Antidiabetic Activity of Chemically Synthetic Compound on Alloxan Induced Diabetes in Mice

Oral supplementation of diabetic mice with propolis restores the proliferation capacity and chemotaxis of B and T lymphocytes towards CCL21 and CXCL12 by modulating the lipid profile, the pro-inflammatory cytokine levels and oxidative stress.

BackgroundType 1 diabetes mellitus (T1D) is a chronic autoimmune disease caused by the selective destruction of pancreatic β cells, followed by hyperglycemia, oxidative stress and the subsequent extensive impairment of immune cell functions, a phenomenon responsible for the development of chronic diabetic complications. Propolis, a natural bee product that is extensively used in foods and beverages, significantly benefits human health. Specifically, propolis exerts antioxidant, anti-inflammatory and analgesic effects that may improve diabetic complications. To further elucidate the potential benefits of propolis, the present study investigated the effect of dietary supplementation with propolis on the plasma cytokine profiles, free radical levels, lipid profile and lymphocyte proliferation and chemotaxis in a streptozotocin (STZ)-induced type I diabetic mouse model.MethodsThirty male mice were equally distributed into 3 experimental groups: group 1, non-diabetic control mice; group 2, diabetic mice; and group 3, diabetic mice supplemented daily with an ethanol-soluble derivative of propolis (100 mg/kg body weight) for 1 month.ResultsFirst, the induction of diabetes in mice was associated with hyperglycemia and significant decreases in the insulin level and the lymphocyte count. In this context, diabetic mice exhibited severe diabetic complications, as demonstrated by a significant decrease in the levels of IL-2, IL-4 and IL-7, prolonged elevation of the levels of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and reactive oxygen species (ROS) and altered lipid profiles compared with control non-diabetic mice. Moreover, antigen stimulation of B and T lymphocytes markedly reduced the proliferative capacity and chemotaxis of these cells towards CCL21 and CXCL12 in diabetic mice compared with control mice. Interestingly, compared with diabetes induction alone, treatment of diabetic mice with propolis significantly restored the plasma cytokine and ROS levels and the lipid profile to nearly normal levels. Most importantly, compared with untreated diabetic mice, diabetic mice treated with propolis exhibited significantly enhanced lymphocyte proliferation and chemotaxis towards CCL21 and CXCL12.ConclusionOur findings reveal the potential immuno-modulatory effects of propolis, which acts as a natural antioxidant to enhance the function of immune cells during diabetes.

Accelerated Type 1 Diabetes Induction in Mice by Adoptive Transfer of Diabetogenic CD4+ T Cells

The nonobese diabetic (NOD) mouse spontaneously develops autoimmune diabetes after 12 weeks of age and is the most extensively studied animal model of human Type 1 diabetes (T1D). Cell transfer studies in irradiated recipient mice have established that T cells are pivotal in T1D pathogenesis in this model. We describe herein a simple method to rapidly induce T1D by adoptive transfer of purified, primary CD4+ T cells from pre-diabetic NOD mice transgenic for the islet-specific T cell receptor (TCR) BDC2.5 into NOD.SCID recipient mice. The major advantages of this technique are that isolation and adoptive transfer of diabetogenic T cells can be completed within the same day, irradiation of the recipients is not required, and a high incidence of T1D is elicited within 2 weeks after T cell transfer. Thus, studies of pathogenesis and therapeutic interventions in T1D can proceed at a faster rate than with methods that rely on heterogenous T cell populations or clones derived from diabetic NOD mice.

Accelerated Type 1 Diabetes Induction in Mice by Adoptive Transfer of Diabetogenic CD4+ T Cells

The nonobese diabetic (NOD) mouse spontaneously develops autoimmune diabetes after 12 weeks of age and is the most extensively studied animal model of human Type 1 diabetes (T1D). Cell transfer studies in irradiated recipient mice have established that T cells are pivotal in T1D pathogenesis in this model. We describe herein a simple method to rapidly induce T1D by adoptive transfer of purified, primary CD4+ T cells from pre-diabetic NOD mice transgenic for the islet-specific T cell receptor (TCR) BDC2.5 into NOD.SCID recipient mice. The major advantages of this technique are that isolation and adoptive transfer of diabetogenic T cells can be completed within the same day, irradiation of the recipients is not required, and a high incidence of T1D is elicited within 2 weeks after T cell transfer. Thus, studies of pathogenesis and therapeutic interventions in T1D can proceed at a faster rate than with methods that rely on heterogenous T cell populations or clones derived from diabetic NOD mice.

Microinflammation in the pathogenesis of diabetic nephropathy.

Diabetic nephropathy is the leading cause of end-stage renal failure in developed countries. Furthermore, diabetic nephropathy is related to the risk of cardiovascular diseases and an increase in mortality of diabetic patients. Several factors are involved in the development of nephropathy, including glomerular hyperfiltration, oxidative stress, accumulation of advanced glycation end-products, activation of protein kinase C, acceleration of the polyol pathway and over-expression of transforming growth factor-β. Recently, accumulated data have emphasized the critical roles of chronic low-grade inflammation, 'microinflammation', in the pathogenesis of diabetic nephropathy, suggesting that microinflammation is a common mechanism in the development of diabetic vascular complications. Expression of cell adhesion molecules, chemokines and pro-inflammatory cytokines are increased in the renal tissues of diabetic patients and animals. Deficiency of pro-inflammatory molecules results in amelioration of renal injuries after induction of diabetes in mice. Plasma and urinary levels of cytokines, chemokines and cell adhesion molecules, are elevated and correlated with albuminuria. Several kinds of drugs that have anti-inflammatory actions as their pleiotropic effects showed renoprotective effects on diabetic animals. Modulation of the inflammatory process prevents renal insufficiency in diabetic animal models, suggesting that microinflammation is one of the promising therapeutic targets for diabetic nephropathy, as well as for cardiovascular diseases.

Dedifferentiation of Immortalized Human Podocytes in Response to Transforming Growth Factor-β

OBJECTIVEDiabetic nephropathy is associated with dedifferentiation of podocytes, losing the specialized features required for efficient glomerular function and acquiring a number of profibrotic, proinflammatory, and proliferative features. These result from tight junction and cytoskeletal rearrangement, augmented proliferation, and apoptosis.RESEARCH DESIGN AND METHODSExperiments were performed in conditionally immortalized human podocytes developed by transfection with the temperature-sensitive SV40-T gene. Cells were then cultured in the presence of transforming growth factor (TGF)-β1 or angiotensin II in the presence or absence of a selective inhibitor of the TGF-β type I receptor kinase, SB-431542. Gene and protein expression were then examined by real-time RT-PCR and immunofluorescence, and correlated with changes observed in vivo in experimental diabetes.RESULTSTreatment of cells with TGF-β1 resulted in dynamic changes in their morphology, starting with retraction and shortening of foot processes and finishing with the formation of broad and complex tight junctions between adjacent podocytes. This dedifferentiation was also associated with dose- and time-dependent reduction in the expression of glomerular epithelial markers (nephrin, p-cadherin, zonnula occludens-1) and increased expression of mesenchymal markers (α−smooth muscle actin, vimentin, nestin), matrix components (fibronectin, collagen I, and collagen IV α3), cellular proliferation, and apoptosis. The induction of diabetes in mice was also associated with similar changes in morphology, protein expression, and proliferation in glomerular podocytes.CONCLUSIONSIn response to TGF-β and other TGF-dependent stimuli, mature podocytes undergo dedifferentiation that leads to effacement of foot processes, morphologic flattening, and increased formation of intercellular tight junctions. This simplification of their phenotype to a more embryonic form is also associated with reentry of mature podocytes into the cell cycle, which results in enhanced proliferation and apoptosis. These “pathoadaptive” changes are seen early in the diabetic glomerulus and ultimately contribute to albuminuria, glomerulosclerosis, and podocytopenia.

Leptin Therapy Reverses Hyperglycemia in Mice With Streptozotocin-Induced Diabetes, Independent of Hepatic Leptin Signaling

OBJECTIVELeptin therapy has been found to reverse hyperglycemia and prevent mortality in several rodent models of type 1 diabetes. Yet the mechanism of leptin-mediated reversal of hyperglycemia has not been fully defined. The liver is a key organ regulating glucose metabolism and is also a target of leptin action. Thus we hypothesized that exogenous leptin administered to mice with streptozotocin (STZ)-induced diabetes reverses hyperglycemia through direct action on hepatocytes.RESEARCH DESIGN AND METHODSAfter the induction of diabetes in mice with a high dose of STZ, recombinant mouse leptin was delivered at a supraphysiological dose for 14 days by an osmotic pump implant. We characterized the effect of leptin administration in C57Bl/6J mice with STZ-induced diabetes and then examined whether leptin therapy could reverse STZ-induced hyperglycemia in mice in which hepatic leptin signaling was specifically disrupted.RESULTSHyperleptinemia reversed hyperglycemia and hyperketonemia in diabetic C57Bl/6J mice and dramatically improved glucose tolerance. These effects were associated with reduced plasma glucagon and growth hormone levels and dramatically enhanced insulin sensitivity, without changes in glucose uptake by skeletal muscle. Leptin therapy also ameliorated STZ-induced hyperglycemia and hyperketonemia in mice with disrupted hepatic leptin signaling to a similar extent as observed in wild-type littermates with STZ-induced diabetes.CONCLUSIONSThese observations reveal that hyperleptinemia reverses the symptoms of STZ-induced diabetes in mice and that this action does not require direct leptin signaling in the liver.

β Cell Protecting and Immunomodulatory Activities of Paecilomyces Hepiali Chen Mycelium in STZ Induced T1DM Mice

The anti-hyperglycemic and immunomodulatory activities of the ethanol extract from Paecilomyces Hepiali Chen (PHC), a Chinese medicine, were investigated in streptozotocin-induced type 1 diabetic (T1DM) mice. Male Balb/c mice, which were i.p. injected with streptozotocin (STZ, 50 mg/kg, for 5 consecutive days) on Day 7, were orally administered saline (the normal control and diabetic control group), Metformin (60 mg/kg, b.w., positive group), or the extract (100 mg/kg, b.w., PHC prevention group) from Day 1 to Day 28, Mice i.p. injected with streptozotocin (STZ, 50 mg/kg, b.w.) for 5 consecutive days prior to PHC treatment (100 mg/kg, b.w.) were used as the PHC treatment group. The effects of PHC on postprandial blood glucose concentrations, plasmatic insulin levels, morphology of pancreatic beta cells and CD4(+) T cells proliferation after 28-day treatment were monitored. Results showed that PHC administered 6 days before STZ induction of diabetes in mice significantly decreased blood glucose level (p < 0.01). An increase of insulin level was also observed as compared to those in the diabetic control group (p < 0.01). In addition, fewer inflammatory cells infiltrated the pancreatic islet and fewer beta cells death by apoptosis within the inflamed islets were observed. More importantly, the CD4(+) T cell proliferation was remarkably attenuated ex vivo in mice preventively treated with PHC (p < 0.01). In comparison to the PHC prevention group, no significant hypoglycemia, changes of insulin level and beta cell protection were observed in mice treated with PHC after STZ administration. Our findings demonstrated that preventive administration of PHC protected beta cells from apoptosis in type 1 diabetes induced by STZ, and the underlying mechanism may be involved in suppressing CD4(+) T cells reaction, reducing inflammatory cells infiltration and protecting beta cell apoptosis in pancreatic islet.

Gene Therapy for Diabetic Neuropathy

Erythropoietin (EPO) has putative neuroprotective effects, but systemic delivery of EPO causes a rise in hematocrit. Now, researchers have tested the effects of a gene therapy approach in a mouse model of diabetic neuropathy. Two weeks after using streptozotocin to induce diabetes in mice, the researchers subcutaneously injected into the mice either placebo or EPO, packaged in a nonreplicating herpes virus. Compared with placebo-treated diabetic mice, those treated with EPO had no increase in hematocrit but had significantly better dermal sensitivity to heat, epidermal nerve terminal density, and sudomotor function in response to pilocarpine, and signifcantly …

Effect of insulin and nimodipin on calcium signals in murine primary afferent neurons with experimental diabetes

The effect of insulin injections and long-term administration of the calcium channel blocker nimodipin on depolarization-induced calcium signals was studied in neurons isolated from the dorsal root ganglia of mice with streptozotocin-induced diabetes. Induction of diabetes in mice was followed by slowing of the calcium signal decay kinetics in small neurons (mainly related to the transmission of nociceptive signals). Subcutaneous insulin injections (1 U/kg) tended to normalize the parameters of calcium signals modified by diabetes. Preliminary 3-week-long peroral administration of nimodipin (40 mg/kg) increased the peak amplitude of depolarization-induced calcium signals in isolated neurons and caused spontaneous activity usually absent in the cells under control conditions. Kinetics of calcium transients in this case remained slow. It was concluded that hyperglycemia and related impairments of the surplus Ca2+ extrusion mechanisms play an essential role in genesis of the changes in calcium signals caused by streptozotocin-induced diabetes.