Cold Exposure Improves the Anti-diabetic Effect of T0901317 in Streptozotocin-Induced Diabetic Mice.
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SUBMITTER: Gao M
PROVIDER: S-EPMC4406970 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundOxidative stress mediates the pathophysiology of diabetic neuropathy (DN) with activation of apoptotic pathway and reduction of autophagy. Arctigenin (ARC) is a natural lignan isolated from some plants of the Asteraceae family that shows antioxidant property. The present study aimed to explore the mechanistic neuroprotective effect of ARC on animal model for DN.MethodsDN was induced using streptozotocin (STZ) at a dose of 45 mg/kg, i.p, for five consecutive days and ARC was administered orally (25 or 50 mg) for 3 weeks. The mechanical sensitivity and thermal latency were determined using von Frey and hotplate, respectively. Beclin, p62, and LC3 were detected as markers for autophagy by western blot. Levels of reduced glutathione, lipid peroxides, and activities of catalase and superoxide dismutase were detected as readout for oxidative stress. Apoptotic parameters and histopathological changes were revealed in all experimental groups.ResultsThe present study showed deterioration of the function and structure of neurons as a result of hyperglycemia. Oxidative stress and impaired autophagy were observed in diabetic neurons as well as the activation of apoptotic pathway. ARC improved the behavioral and histopathological changes of diabetic mice. ARC combated oxidative stress through diminishing lipid peroxidation and improving the activity of antioxidant enzymes. This was concomitant by reducing the biomarkers of apoptosis. ARC augmented the expression of Beclin and LC3 while it lessened the expression of p62 indicating the activation of autophagy. These findings suggest that ARC can ameliorate DN by combating apoptosis and oxidative stress and improving autophagy.
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Project description:Aims: To evaluate the protective effects of exogenous pancreatic kallikrein (PKK) treatment on diabetic cardiomyopathy (DCM) and explore the underlying mechanisms. Methods and Results: Streptozotocin (STZ)-induced diabetic rats, a type 1 diabetic model, were treated with either PKK or saline for 12 weeks. Non-diabetic rats were used as controls. PKK administration attenuated the mitochondria swelling, Z line misalignments, myofibrosis and interstitial collagen accumulation in diabetic myocardial tissue. The oxidative stress imbalance including increased nitrotyrosine, decreased anti-oxidative components such as nuclear receptor nuclear factor like 2 (Nrf2), glutathione peroxidase 1(GPx-1), catalase (CAT) and superoxide dismutase (SOD), were recovered in the heart of PKK-treated diabetic rats. In diabetic rats, protein expression of TGF-?1 and accumulation of collagen I in the heart tissues was decreased after PKK administration. Markers for inflammation were decreased in diabetic rats by PKK treatment. Compared to diabetic rats, PKK reversed the degradation of I?B-?, an inhibitive element of heterotrimer nuclear factor kappa B (NF-?B). The endothelial nitric oxide synthase (eNOS) protein and myocardial nitrate/nitrite were impaired in the heart of diabetic rats, which, however, were restored after PKK treatment. The sarcoplasmic reticulum Ca2+-ATPase 2 (SERCA2) and phospholamban (PLN) were mishandled in diabetic rats, while were rectified in PKK-treated diabetic rats. The plasma NT-proBNP level was increased in diabetic rats while was reduced with PKK treatment. Conclusion: PKK protects against DCM via reducing fibrosis, inflammation, and oxidative stress, promoting nitric oxide production, as well as restoring the function of the calcium channel.
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Project description:Background:Lens culinari s Medik seed has been used in traditional practices to treat various ailments, including diabetes mellitus, in Ethiopia. Previous phytochemical screening studies indicated that germination of the seed of L. culinaris contains more bioactive constituents compared to raw seeds. The aim of this study was to investigate the antidiabetic activity of an aqueous methanol extract of germinated L. culinaris seed extract in streptozotocin (Stz)-induced diabetic mice. Methods:The antidiabetic effect of germinated L. culinaris seed extract was determined using Stz-induced diabetic mice. An 80% aqueous methanol extract of germinated L. culinaris seed at doses of 100, 200, and 400 mg/kg was used in the treatment group. Glibenclamid (5 mg/kg) and dimethyl sulfoxide 2% were used as positive and negative controls, respectively. The test extract and controls were given daily for 3 weeks. Blood-glucose levels and body-weight changes were measured weekly. Lipid-profile levels were measured at the end of each experiment. Oral glucose-tolerance tests were performed to evaluate the postprandial effect of the extract. Results:The aqueous methanol extract of germinated L. culinaris significantly reduced blood-glucose levels and increased body weight (p<0.05). The extract also improved serum-lipid profiles in diabetic mice after 21 days (p<0.05). The seed extract also resulted in significant reductions in blood-glucose levels after an oral glucose load in normal mice (p<0.05). Conclusion:An aqueous methanol extract of germinated L. culinaris seed has both antidiabetic and antihyperlipidemic effects.
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Project description:Hyperglycemia impairs immune response; however, it remains unknown whether the anti-tumor effects of anti-programmed cell death-1 antibody (PD-1-Ab) treatment are changed in hyperglycemic conditions. We analyzed the effect of PD-1-Ab on tumor growth in streptozotocin-induced diabetic mice (STZ-mice) subcutaneously inoculated with MC38 (a colon carcinoma cell line). Furthermore, we assessed the expression of chemokines by polymerase chain reaction (PCR) array in tumor-draining lymph nodes (dLNs) of these mice and MC38 cells cultured in different glucose concentrations. The suppressive effect of PD-1-Ab on tumor growth was attenuated. This was accompanied by fewer tumor-infiltrating CD8+ T cells, and STZ-mice had fewer tumor-infiltrating CD11c+ dendritic cells (DCs) than normoglycemic mice. mRNA expression levels of CXCL9, a chemokine recruiting CD8+ T cells, were lower in dLNs of STZ-mice than in normoglycemic mice after PD-1-Ab treatment, and its protein was expressed in DCs. In MC38 cells cultured with 25 mM glucose, mRNA expression of CCL7, a chemokine recruiting DCs, was decreased compared to cells cultured with 5 mM glucose. These results suggest that the STZ-induced hyperglycemia impairs the effect of PD-1-Ab treatment on MC38 tumor growth, and is accompanied by reduced infiltration of DCs and CD8+ T cells and decreased expression of CCL7 and CXCL9.
| S-EPMC10097709 | biostudies-literature
Project description:Glucagon-like peptide 1 (GLP-1) mimetics have been approved as an adjunct therapy for glycemic control in type 2 diabetic patients for the increased insulin secretion under hyperglycemic conditions. Recently, it is reported that such agents elicit neuroprotective effects against diabetes-associated cognitive decline. However, there is an issue of poor compliance by multiple daily subcutaneous injections for sufficient glycemic control due to their short duration, and neuroprotective actions were not fully studied, yet. In this study, using the prepared exendin-4 fusion protein agent, we investigated the pharmacokinetic profile and the role of this GLP-1 mimetics on memory deficits in a high-fat diet (HFD)/streptozotocin (STZ) mouse model of type 2 diabetic mellitus. After induction of diabetes, mice were administered weekly by intraperitoneal injection of GLP-1 mimetics for 6 weeks. This treatment reversed HFD/STZ-induced metabolic symptoms of increased body weight, hyperglycemia, and hepatic steatosis. Furthermore, the impaired cognitive performance of diabetic mice was significantly reversed by GLP-1 mimetics. GLP-1 mimetic treatment also reversed decreases in GLP-1/GLP-1 receptor expression levels in both the pancreas and hippocampus of diabetic mice; increases in hippocampal inflammation, mitochondrial fission, and calcium-binding protein levels were also reversed. These findings suggest that GLP-1 mimetics are promising agents for both diabetes and neurodegenerative diseases that are associated with increased GLP-1 expression in the brain.
| S-EPMC7076426 | biostudies-literature
Project description:Diabetes mellitus has reached epidemic proportion worldwide. One of the diabetic complications is cardiomyopathy, characterized by early left ventricular (LV) diastolic dysfunction, followed by development of systolic dysfunction and ventricular dilation at a late stage. The pathogenesis is multifactorial, and there is no effective treatment yet. In recent years, 4-hydroxy-2-nonenal (4-HNE), a toxic aldehyde generated from lipid peroxidation, is implicated in the pathogenesis of cardiovascular diseases. Its high bioreactivity toward proteins results in cellular damage. Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is the major enzyme that detoxifies 4-HNE. The development of small-molecule ALDH2 activator provides an opportunity for treating diabetic cardiomyopathy. This study found that AD-9308, a water-soluble andhighly selective ALDH2 activator, can improve LV diastolic and systolic functions, and wall remodeling in streptozotocin-induced diabetic mice. AD-9308 treatment dose-dependently lowered serum 4-HNE levels and 4-HNE protein adducts in cardiac tissue from diabetic mice, accompanied with ameliorated myocardial fibrosis, inflammation, and apoptosis. Improvements of mitochondrial functions, sarco/endoplasmic reticulumcalcium handling and autophagy regulation were also observed in diabetic mice with AD-9308 treatment. In conclusion, ADLH2 activation effectively ameliorated diabetic cardiomyopathy, which may be mediated through detoxification of 4-HNE. Our findings highlighted the therapeutic potential of ALDH2 activation for treating diabetic cardiomyopathy.
| S-EPMC7998151 | biostudies-literature
Project description:PurposeThe current study aimed to determine the antidiabetic effects of leaf extract of Ficus asperifolia in streptozotocin-induced diabetic rats.MethodsA total of ninety-five (95) adult rats were used for the experiment. The whole study protocol was divided into three sets of individual experiments. The animals were divided randomly into seven groups of five rats each. The rats were given a diet supplemented with 50 g high fat to 50 g vital feeds for two weeks. The study lasted 28 days with daily administration and weekly blood glucose and body weight check. At the end of the experiment protocol, the rats were fasted overnight and were anesthetized. Blood was collected via cardiac puncture from each animal for biochemical analysis. Metglim 3.38 mg/kg bodyweight was used as positive control. Diabetes was induced using streptozotocin (35 mg/kg in 0.1 M phosphate-buffered saline) intraperitoneally for 5 days. Phytochemicals were analyzed in both extract and fractions.ResultsPhytochemical screening revealed the presence of alkaloids, saponins, flavonoids, glycosides, tannins, carotenoids, terpenes, and steroids in both extract and fractions. Proteins, carbohydrates, and fats were detected by systematic molecular analysis. Fraction 1 of plant extracts prevented glucose-induced hyperglycaemia 30 min' post glucose load in all rats. Streptozotocin treatment caused a significant increase (p˂0.05) in blood sugar, total cholesterol, triacylglycerol, low-density lipoproteins and a significant (p˂0.05) decrease in food intake, body weight and high-density lipoproteins in diabetic rats.ConclusionTreatment with the extract significantly improved the derangements caused by streptozotocin. These results suggest that the leaf extracts of Ficus asperifolia could serve as a potential treatment for diabetes therapy.
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Project description:BackgroundDipeptidyl peptidase-4 (DPP-4) inhibitors are widely used in the treatment of patients with type 2 diabetes and have proven protective effects on diabetic kidney disease (DKD). Whether DPP-4 inhibitors have renoprotective effects on insulin-deficient type 1 diabetes has not been comprehensively examined. The aim of this study was to determine whether gemigliptin, a new DPP-4 inhibitor, has renoprotective effects in streptozotocin (STZ)-induced type 1 diabetic mice.MethodsDiabetes was induced by intraperitoneal administration of a single dose of STZ. Mice with diabetes were treated without or with gemigliptin (300 mg/kg) for 8 weeks. Morphological changes of the glomerular basement membrane (GBM) were observed by electron microscopy and periodic-acid Schiff staining. In addition, we measured blood glucose and urinary albumin excretion and evaluated fibrotic markers using immunohistochemical staining, quantitative reverse transcription polymerase chain reaction analysis, and Western blot analysis.ResultsGemigliptin did not reduce the blood glucose levels of STZ-treated mice. In gemigliptin-treated mice with STZ, a significant reduction in urinary albumin excretion and GBM thickness was observed. Immunohistological examination revealed that gemigliptin attenuated renal fibrosis induced by STZ and decreased extracellular matrix protein levels, including those of type I collagen and fibronectin, and Smad3 phosphorylation. In cultured rat renal cells, gemigliptin inhibited transforming growth factor β-stimulated type I collagen and fibronectin mRNA and protein levels via down-regulation of Smad3 phosphorylation.ConclusionOur data demonstrate that gemigliptin has renoprotective effects on DKD, regardless of its glucose-lowering effect, suggesting that it could be used to prevent DKD, including in patients with type 1 diabetes.
| S-EPMC4929225 | biostudies-literature
Project description:Type-1 Diabetes Mellitus (T1DM) is regarded as a multifunctional, immune-related disease which causes massive destruction of islet β-cells in pancreas resulting in hyperglycemic, hypoinsulinemia and hyperlipidimic conditions. The aim of the present study, was to investigate the hypothesis that streptozotocin (STZ)-induced T1DM in Balb/c mice when treated with crude polysaccharide from seaweed, Dictyopteris divaricata (CDDP) depicts improvement in diabetes-related symptoms. Treatment with CDDP resulted in decreased body weight loss, improved food consumption and water intake disbalances. The CDDP effectively improved fasting blood glucose, oral glucose tolerance (OGTT), serum insulin, insulin secretion, rejuvenation of β-cells mass, serum lipid profile and pro-inflammatory cytokines levels. Additionally, treatment with CDDP increased the population of beneficial bacteria such as Firmicutes, Bacteroidetes and Lactobacillus at phylum, family and genus levels by 16S rRNA sequencing. Furthermore, immunohistological examination confirmed that CDDP reduces the inflammation and restored the structural morphology of colon and upraised the levels of insulin receptor substrate-1 (IRS-1), Mucin-2 (MUC-2) and tight-junction proteins (TJs) whereby maintaining the gut structures and barrier permeability. Thus, the above presented data, highlights the safe and therapeutic effects of crude polysaccharide (CDDP) from D. divaricata in the treatment and restoration of T1DM disorders and can be used as a food supplement alternative to diabetes medicine.
| S-EPMC9482207 | biostudies-literature
Project description:The study was designed to investigate the anti-hyperglycemic activity of selenium nanoparticles (SeNPs) in streptozotocin-induced diabetic rats. Fifty-five mg/kg of streptozotocin was injected in rats to induce diabetes. Animals either treated with SeNPs alone or with insulin (6 U/kg) showed significantly decreased fasting blood glucose levels after 28 days of treatment. The serum insulin concentration in untreated diabetic animals was also enhanced by SeNPs. The results demonstrated that SeNPs could significantly decrease hepatic and renal function markers, total lipid, total cholesterol, triglyceride and low-density lipoprotein cholesterol levels, and glucose-6-phosphatase activity. At the same time, SeNPs increased malic enzyme, hexokinase and glucose-6-phosphate dehydrogenase activity, liver and kidney glycogen contents, and high-density lipoprotein cholesterol levels. In addition, SeNPs were able to prevent the histological injury in the hepatic and renal tissues of rats. However, insulin injection also exhibited a significant improvement in diabetic animals after 28 days of treatment. This study suggests that SeNPs can alleviate hyperglycemia and hyperlipidemia in streptozotocin-induced diabetic rats, possibly by eliciting insulin-mimetic activity.
| S-EPMC4631434 | biostudies-literature