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1.
AIM: To explore the effect of CXCL16 deficiency on streptozocin (STZ)-induced diabetic nephropathy in mice. METHODS: CXCL16 knockout (C16 KO) mice (8 years old) were used to build up diabetes model by treating with STZ.Age- and gender-matched wild-type (WT) C57BL/6J mice treated with STZ were used as control. All mice were fed with chow diets for 12 weeks, and the development of diabetic nephropathy was evaluated. RESULTS: Compared with the WT mice treated with STZ, C16 KO mice treated with STZ presented lower fasting glucose levels and better glucose tolerance power. C16 KO mice treated with STZ also had lower urine protein levels and smaller areas of glomerular injury as compared with WT mice treated with STZ. Furthermore, CXCL16 deficiency decreased the contents of renal reactive oxygen species (ROS), malondialdehyde (MDA) and oxidized low-density lipoprotein (ox-LDL) and the mRNA expression of lectin-like oxidized low-density lipoprotein receptor 1 (Lox-1), and attenuated the expression of renal inflammatory factors including tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6), as well as chemokines including intercellular cell adhesion molecular 1 (ICAM-1) and chemokine C-X-C motif ligand 1 (CXCL1). CONCLUSION: CXCL16 deficiency obviously inhibits the development of STZ-induced diabetic nephropathy in mice.  相似文献   

2.
HUANG Tian  CAI Xi  ZHONG Ling 《园艺学报》2017,33(8):1460-1466
AIM: To investigate the effect of epidermal growth factor receptor (EGFR) inhibitor erlotinib on kidney injury in diabetic nephropathy (DN) rat and the underlying mechanism. METHODS: The rat model of DN was induced by intraperitoneal injection of streptozotocin (STZ) at dose of 55 mg/kg. One week after STZ injection, the rats with blood glucose level exceeding 16.7 mmol/L were identified as diabetic. Diabetic rats were randomly divided into 2 groups:STZ group and STZ+erlotinib group. In addition, the normal rats were used as control group. The rats in STZ+erlotinib group were treated with erlotinib at 100 mg·kg-1·d-1 for 4 weeks(5th~8th week). The fasting blood glucose (FBG), serum creatinine (SCr) and 24 h urine protein were measured. The pathological changes of the kidney were observed by HE staining and Masson staining. The protein levels of EGFR, p-EGFR, transforming growth factor β1 (TGFβ1), Smad2/3, p-Smad2/3, collagen Ⅳ (ColⅣ) and fibronectin in the kidney tissues were determined by Western blot. The reactive oxygen species (ROS) level and malondialdehyde (MDA) content in the renal tissues were futher analyzed. RESULTS: Compared with control group, the levels of FBG, 24 h urine protein and Scr were significantly increased in STZ group (P<0.01). Compared with STZ group, the levels of FBG, 24 h urine protein and SCr in STZ+erlotinib group were markedly decreased (P<0.05). In additon, the glomerular structure was restored to normal, the proliferative degree of mesangial cells markedly attenuated, and the epithelial cells were in alignment in STZ+erlotinib group. Moreover, erlotinib significantly inhibited the protein levels of p-EGFR, TGFβ1, p-Smad2/3, ColⅣ and fibronectin in the kidney tissues of STZ rats. In addition, erlotinib also significantly inhibited the levels of ROS and MDA in the kidney tissues of STZ rats. CONCLUSION: Erlotinib ameliorates STZ-induced diabetic nephropathy possibly through inhibiting the activation of EGFR/TGFβ1-Smad2/3 signaling pathway in association with suppression of fibrosis and oxidative stress.  相似文献   

3.
AIM: To investigate the effects of dexamethasone(DEX) on the pancreatic endocrine function when steroid diabetes mellitus(SDM) occurred. METHODS: 140 rats were randomly assigned to 4 groups according to the clinic doses of DEX administration, Radioimmunoassay and in situ hybridization were applied to evaluate islet hormone changes in pancreas and blood.RESULTS: Changes in fasting blood glucose(FBG) 、fasting serum insulin(FINS) caused by DEX were dose and time-dependent. Changes in somatostatin(SS)mRNA and protein in islet as well as FINS occurred earlier than that of FBG. CONCLUSION: The super-physiological DEX influenced the expression SS and insulin secretion in islet, which may play an important role in SDM.  相似文献   

4.
AIM:To investigate the effect of insulin signaling on the development of Alzheimer disease (AD) and to explore its potential mechanisms. METHODS:The rats were treated with streptozotocin (STZ, 3 mg/kg) intracerebroventricularly (ICV) at the 1st day and the 3rd day of the experiment to induce dementia model. Twenty-one days after the injection of STZ at the 1st day, spatial learning and memory of the rats were determined by Morris water maze test. The expression levels of insulin-degrading enzyme (IDE), glycogen synthase kinase 3β (GSK-3β), phosphorylated GSK-3β (p-GSK-3β), tau and phosphorylated tau (p-tau) were measured by Western blotting. The levels of amyloid β-proteins (Aβ1-40 and Aβ1-42) in the brain of the rats were detected by the method of immunohistochemistry. The mRNA levels of insulin, insulin receptor, tau and IDE were measured by real-time RT-PCR. RESULTS:ICV-STZ deteriorated the abilities of spatial learning and memory of the rats and reduced the activity of IDE and the mRNA levels of insulin and insulin receptor. STZ treatment enhanced GSK-3β activity and tau phosphorylation. The levels of Aβ1-40 and Aβ1-42 in cerebral cortex were significantly increased in the rats treated with STZ. CONCLUSION:ICV-STZ results in AD-like behaviors and pathological changes via damaging the brain insulin signaling, indicating that insulin signaling may play important roles in the AD pathogenesis.  相似文献   

5.
AIM: To investigate the role of peroxisome proliferator-activated receptors (PPARs)-inflammation signaling pathways in diabetic hepatopathy. METHODS: Diabetic mouse model was established by feeding the mice with a high-energy diet for 4 weeks combined with intraperitoneal injection of streptozotocin (STZ; 40 mg·kg-1·d-1 for 5 d). The hepatopathy model was confirmed by histopathological observation and the indexes of liver function, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP), after another 4 weeks. Moreover, fasting blood glucose (FBG), and serum levels of total cholesterol (TC), triglyceride (TG) and insulin were measured, and the HOMA insulin resistance index (HOMA-IR) was calculated. The mRNA and protein expression levels of PPARs and inflammation-related factors were measured by qPCR and Western blot, respectively. RESULTS: After treatment with STZ for 7 d, the FBG of mice exceeded 11.1 mmol/L, suggesting that the diabetic model was established. After 4 weeks, the structural deformation of the hepatocytes (including hepatocytes containing abundant fat vacuoles, and inflammatory cell infiltration), and the increases in the serum levels of insulin, HOMA-IR, TC, TG, ALT, AST and ALP were observed (P<0.01), indicating the occurrence and progression of hepatopathy in diabetic mice. Meanwhile, compared with the control group, the mRNA and protein expression of PPARα, PPARβ and PPARγ decreased, but the expression of nuclear factor-κB (NF-κB), cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) significantly increased in the diabetic hepatopathy mice (P<0.01). CONCLUSION: Down-regulation of PPARα, PPARβ and PPARγ and activation of NF-κB-COX-2/iNOS signaling pathways may be involved in the diabetic hepatopathy in mice induced by long-term high-energy diet feeding combined with intraperitoneal injection of STZ.  相似文献   

6.
AIM: To study rhIL-1β effects on fetal islet function and IL-6 production in vitro METHODS: Islets from fetal pancreas was separated by collagenase type V (0.5 mg/mL) and cultured in vitro The islets were exposed to culture medium alone for 48 h or with different concentration of rhIL-1β The supernatants of culture of human fetal islets were assayed for IL-6, insulin and glucagon RESULTS:(1) IL-6 activity was increased 4 0 folds (74-294 mU/islet) when islets were exposed to rhIL-1β(20U/mL); (2) IL-6 McAb significantly reduced IL-6 activity in islet supernatants from control group or islet exposed to rhIL-1β treated group; (3)IL-6 mRNA in human fetal islet exposed to rhIL-1β is higher than control in dot hybridization; (4) Soluble insulin and cellular insulin within islet released to supernatants was slightly decreased (0.48~0.78 IU/islet and 0.65~0.79 IU/islet); (5) Glucagon secretion was significantly increased 3.2 folds (1.0~3.2 pg/islet) CONCLUSION: Pancreatic islets produce IL-6 is up-regulated by rhIL-1β On the other hand, Il-6 produced by the islet may act as a costimulator for autoreactive B and T lymphocytes in autoimmune diabetes.  相似文献   

7.
AIM: To investigate the effects of total triterpenoids from Psidium guajava leaves (TTPGL) on blood glucose and lipids in type 2 diabetic rats. METHODS: The diabetic rats were induced by intraperitoneal injection of streptozotocin at dose of 35 mg/kg and feeding with high-fat diet. The animals were divided into 5 groups: diabetic model control group (model), TTPGL treatment groups (with the doses of 60, 120 and 240 mg/kg, respectively) and rosiglitazone treatment group (3 mg/kg). Another 12 normal SD rats were used as the normal controls. The rats received daily treatment for 6 weeks, and then the levels of fasting blood glucose (FBG), fasting insulin (FINS), triglyceride (TG), total cholesterol (TCH), free fatty acid (FFA), glycosylated hemoglobin (GHb) and glycosylated serum proteins (GSP) were measured. The protein expression of peroxisome proliferator-activated receptor γ (PPARγ) in adipose tissues was detected by Western blotting. RESULTS: Compared with normal control group, the levels of FBG, GHb and blood lipids were increased in type 2 diabetic rats. The FINS, insulin sensitivity index, and the protein expression of PPARγ in adipose tissues were decreased. Compared with model group, the levels of FBG and GSP were decreased,and the FINS, insulin sensitivity index, and the protein expression of PPARγ in adipose tissues significantly increased in TTPGL treatment groups (with the doses of 120 and 240 mg/kg). The levels of serum TG,TCH and FFA were significantly lower in TTPGL treatment groups (P<0.01 or P<0.05) as compared with the model controls. CONCLUSION: TTPGL decreases the levels of blood glucose and lipids in diabetic rats. TTPGL also increases serum insulin level and improves insulin sensitivity. The action mechanism of TTPGL may be related to the increase in the protein expression of PPARγ.  相似文献   

8.
AIM: To investigate the effect of non-alcoholic fatty liver disease (NAFLD) on metabolic syndrome (MS)- related type 2 diabetes. METHODS: Sixty-four rats were randomly divided into 8 groups: normal control groups of 3 months (3NC), 6 months (6NC), 9 months (9NC) and 12 months (12NC), and high-sucrose and high-fat groups of 3 months (3H), 6 months (6H), 9 months (9H) and 12 months (12H). The serum levels of alanine transaminase (ALT), free fatty acid (FFA), endotoxin (LPS), tumor necrosis factor alpha (TNFα), C-reactive protein (CRP), monocyte chemotactic protein-1 (MCP-1), fasting plasma glucose (FPG) and fasting plasma insulin (FINS) were measured. The insulin resistance index (HOMA-IR) and beta cell function index(HOMA-β) were also calculated. The specimens of liver and pancreas were prepared for microscopic observation with HE and Sudan Ⅳ staining. The visceral adipose specimens were also prepared with HE staining. The apoptosis of islet cells was detected by TUNEL.RESULTS: Compared with normal control groups, the levels of ALT, FFA, LPS, TNFα, CRP, MCP-1, FPG, FINS and HOMA-IR in high-sucrose and high-fat groups of every phase were higher, but the level of HOMA-β in 6H group showed a compensatory increase first and then progressively decreased. Compared with normal control groups, TUNEL results showed that the number of apoptotic islet cells in high-sucrose and high-fat groups gradually increased from the 3rd to the 12th month. CONCLUSION: The NAFLD plays a trigger role in the start of MS-related type 2 diabetes.  相似文献   

9.
AIM: To differentiate bone marrow mesenchymal stem cells (BMSCs) into functional insulin-producing cells to produce sufficient pancreatic islet cells for transplantation. METHODS: Recombinant adenovirus vectors carrying PDX1 and NKX6.1 genes were constructed and the bone marrow mesenchymal stem cells were infected by the recombinant adenovirus combined with several cytokines for differentiation. The expressions of PDX1, NKX6.1 and insulin and C-peptide in the differentiated bone marrow mesenchymal stem cells were detected by RT-PCR and Western blotting. After the differentiated bone marrow mesenchymal stem cells were transplanted into subrenal capsule of diabetic mice, cell morphology of the grafts as well as their secretion of insulin and C-peptide were detected. Besides, regulating capacities of grafts on the blood glucose level of the diabetic mice were also detected. RESULTS: BMSCs induced by recombinant adenovirus (pAdxsi-CMV-PDX1/CMV-NKX6.1) and several cytokines showed positive dithizone staining and the expressions of β-cell related molecule such as insulin and glucose transporter 2 were detected by RT-PCR, which showed a sustaining and stable expression. The similar results were showed by Western blotting, immunohistochemical staining and indirect immunofluorescence. The insulin secretions in the cells stimulated with glucose at concentrations of 5.5 and 25 mmol/L in the experimental group were (1 240.4±109.3) mU/L and (3 539.8±245.1) mU/L, respectively, and were significantly higher than those in control group. Moreover, transplantation of the cells to STZ mice in treatment group made serum glucose recover to normal level. CONCLUSION: PDX1 and NKX6.1 gene-modified bone marrow mesenchymal stem cells differentiate into insulin-producing cells in vitro. When these cells transplanted into STZ induced diabetic mice, their serum glucose could return to the normal level and they could live well. Thus this is a promising method for diabetes treatment.  相似文献   

10.
AIM: To discuss the effects of vasoconstrictor and endothelium-dependent relaxation agent on the thoracic aortic rings in different stages of diabetes mellitus. METHODS: Streptozotocin (STZ, 40 mg/kg) was injected intraperitoneally to establish diabetic model in C57BL/6J mice. At the 17th, 22nd, 28th week, diabetic and age-matched control mice were sacrificed respectively and the effects of vasoconstrictors: phenylephrine (PE), 60 mmol/L KCl and endothelium-dependent relaxation agent respectively (ACh) were measured in two groups using thoracic aortic rings. RESULTS: The level of fasting plasma glucose concentration 2 weeks after STZ treatment increased higher (≥11.1 mol/L) in STZ-induced diabetic mice than that in age-matched controls, and maintained at this level in entire experiment course. On the contrary, the weight was decreased significantly. The responses of thoracic aortic rings in STZ-induced diabetic mice to PE were increased, unaltered and increased at the 17th, 22nd, 28th weeks, respectively compared to that in age-matched controls. The responses to 60 mmol/L KCl were also increased in all stages. While the responses to ACh were increased, unaltered and decreased at the 17th, 22nd, 28th weeks, respectively compared to that in age-matched controls. CONCLUSION: The responses of thoracic aortic rings to vasoconstrictor enhance in STZ-induced diabetic mice. However, the endothelial functions potentiate initially due to compensation, and then lower exhibiting endothelial damage.  相似文献   

11.
AIM: To investigate whether L-carnitine (LC) treatment confers renoprotection in a rat model of streptozotocin (STZ)-induced diabetic nephropathy (DN). METHODS: Diabetic animal model was established by intraperitoneal injection of STZ (65 mg/kg) in Sprague-Dawley rats. Diabetic rats were treated with LC (50 mg·kg-1·d-1 or 200 mg·kg-1·d-1 intravenously) daily for 12 weeks. The effects of LC on STZ-induced DN were evaluated by assessing renal function, urinary protein excretion, histopathological changes, macrophage infiltration, the expression of proinflammatory and prosclerotic cytokines, and the expression of nuclear factor-κB (NF-κB) and apoptosis-related gene. RESULTS: LC administration significantly decreased glomerulosclerosis, preserved the number of podocytes, and reduced macrophage infiltration. These changes were accompanied by improvements in urinary protein excretion and renal dysfunction. LC treatment suppressed the expression of proinflammatory and prosclerotic cytokines, and these changes were paralleled by significant attenuation of NF-κB and apoptosis-related gene expression. CONCLUSION: LC has a renoprotective effect against STZ-induced DN in rats.  相似文献   

12.
AIM: To investigate the intervention effect of pentoxifylline (PTX) on type 1 diabetes mellitus in non-obese diabetic (NOD)mice and explore its possible mechanism.METHODS: Eight-week-old NOD mice were treated with PTX to investigate the incidence of cyclophosphamide accelerating diabetes.The apoptosis of beta-cells was detected by TUNEL,the expressions of caspase-3 in islet of the NOD mice was checked by immunohistochemistry and the expressions of caspase-8 was determined by RT-PCR.RESULTS: The incidence of diabetes in PTX group was 40.63%,which was obviously lower than 69.70% in the control group (P<0.05). Apoptosis index of beta-cells was 4.80% in PTX group and was 9.04% in control group,of which the former was lower than the latter (P<0.01).The expression of caspase-3 in islet of the mice in PTX group was much lower than that in control group,and the expression of caspase-8 mRNA in pancreas in PTX group were also markedly lower than that in control group (P<0.01).CONCLUSION: PTX prevents NOD mice from developing type 1 diabetes,which may be related to the downregulation of caspase-3 and caspase-8 expressions in pancreas and then the decrease of beta-cell apoptosis.  相似文献   

13.
AIM: To investigate the effects of tetramethylpyrazine combined with aminoguanidine on the renal functions of neonatal-0 streptozotocin-induced (n0-STZ) rats. METHODS: Neonatal Wistar rats were intraperitoneally injected with a single dose of streptozotocin (STZ) to establish the n0-STZ rat model. The n0-STZ rats were divided into 4 groups: normal control group, insulin resistance group, metformin treatment group and tetramethylpyrazine+aminoguanidine treatment group. Fasting plasm glucose, fasting insulin, insulin resistance index, blood urea nitrogen, serum creatinine, urine albumin and glomerular filtration rate were measured at the 32nd week. The mRNA content of inducible nitric oxide synthase (iNOS) in peripheral blood leukocytes was detected by the technique of in situ hybridization. Nitric oxide (NO) concentration, iNOS activity, the protein expression of iNOS and 3-nitrotyrosine(3-NT) were also assessed in the renal tissues. RESULTS: At the 8th week after the administration of STZ, 82.5% of Wistar rats showed that the fasting plasm glucose level was ≥7.0 mmol/L and the renal functions were seriously damaged. Although both metformin and the combined treatment reduced fasting plasm glucose, fasting insulin and insulin resistance index, the combined treatment was superior in improving the insulin resistance. The damaged renal functions were improved by the combined treatment as reducing blood urea nitrogen and creatinine, increasing glomerular filtration rate were observed. Furthermore, the combined treatment reduced NO concentration, decreased iNOS activity and diminished mRNA content of iNOS, resulting in depressing the generation of 3-NT and iNOS, which surpassed the treatment of metformin. CONCLUSION: Tetramethylpyrazine combined with aminoguanidine improves the renal functions of n0-STZ rats by depressing nitrative stress and enhancing the effect of metformin.  相似文献   

14.
AIM: To investigate the ultrastructural changes of islet microvascular endothelial cells in STZ-induced type 1 diabetic mice. METHODS: BALB/c mice were randomly divided into diabetic group and control group. The expression of insulin and platelet-endothelial cell adhesion molecule-1 (CD31) in islet microvessels was detected by immunohistochemical staining. The ultrastructural changes of islet β cells and islet microvessels were observed under transmission electron microscope. RESULTS: Compared with control group, the number of islet β cells, ratio of β cells/α cells, average number of secretory granules in β cells and insulin expression area per islet in diabetic group were significantly decreased (P<0.01). Besides, diabetic group had fewer microvessels with lower expression of CD31 (P<0.01). Mitochondria in islet microvascular endothelial cells and pericytes in diabetic group were swelling. The basement membrane of islet microvessels became thicker in diabetic group (P<0.01). CONCLUSION: Islet microvascular endothelial cells were impaired in type 1 diabetic mice.  相似文献   

15.
AIM: To study the effects of curcumin (Cur) on diabetic cardiomyopathy (DCM) in rats. METHODS: Male Wistar rats (n=75) were divided into control group and diabetes model group, in which the rats were fed with high-fat diet and then intraperitoneally injected with streptozotocin (STZ, 40 mg/kg). Fasting blood glucose was measured 72 h and 1 week after STZ injection. The diabetic rats were diagnosed when sustained fasting blood glucose levels ≥ 11.6 mmol/L. The diabetic rats were randomly divided into DCM group, DCM+Cur 100 mg/kg group and DCM+Cur 200 mg/kg group. After treatment for 16 weeks, glutathione peroxidase (GSH-Px) activity and malondialdehyde (MDA) level were measured, and the level of cardiac troponin I (cTnI) in the serum was determined by enzyme-linked immunosorbent assay. The protein expression of protein kinase C (PKC) was detected by Western blotting. RESULTS: Curcumin significantly decreased the blood glucose level, increased the body weight, inhibited MDA content and up-regulated the GSH-Px activity in the diabetic rats. Furthermore, curcumin treatment inhibited the diabetes-induced protein expression of PKC. CONCLUSION: Curcumin may have a protective effect on diabetic cardiomyopathy by attenuating oxidative stress.  相似文献   

16.
AIM:To observe the effects of taurine-zinc (TZC) on the learning and memory abilities of vascular dementia (VD) mice and to investigate the related mechanism. METHODS:The mice were randomly divided into model group, sham group, and TZC at 50 mg/kg, 100 mg/kg and 200 mg/kg groups. The mice in drug groups were given TZC by gavage at 10 mL/kg once daily. The mice in sham group and model group were given equal volume of distilled water. VD mice were established by intercepting both common carotid arteries and bleeding at caudal vein after 14 d of gavage. The levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were detected by ELISA. The levels of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) were measured via spectrophotometer. Step-down test and Morris water maze test were used to examine the abilities of learning and memory in the mice. RESULTS:TZC at 50 mg/kg, 100 mg/kg and 200 mg/kg reduced the levels of TNF-α, IL-1β, iNOS and NO in the brain tissues. In the water maze test, TZC at 100 mg/kg and 200 mg/kg significantly decreased the error times and latency compared with model group. In the step-down test, the escape latency was prolonged and error times were lowered significantly by treatment with TZC at 50 mg/kg, 100 mg/kg and 200 mg/kg as compared with model group. CONCLUSION:TZC improves the abilities of learning and memory, which might be related to the reduction of TNF-α, IL-1β, iNOS and NO levels in VD mice.  相似文献   

17.
YANG Qing-yu  GAO Na 《园艺学报》2016,32(9):1627-1634
AIM: To observe the anti-apoptosis effect of liraglutide on the islet through microRNA-375 (miR-375) for providing additional pharmacodynamic evidence for its clinical application. METHODS: For in vitro study, C57BL/KsJ-db/m mice aged 8 weeks served as normal control group. A total of 40 male genetically diabetic C57BL/KsJ-db/db mice at the same age were randomly divided into diabetic control group (the db/db mice were injected subcutaneously with equivalent amount of saline) and liraglutide group (the db/db mice were injected subcutaneously with liraglutide at dose of 300 μg·kg-1·d-1). After 8 weeks of administration, body weight (BW) was measured and blood was collected for detection of fasting blood glucose (FBG), fasting blood insulin (FINS), triglyceride (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). Before sacrifice, intraperitoneal glucose tolerance test (IPGTT) and insulin tolerance test (ITT) were conducted. The histopathological features in the islet tissue were examined with HE staining. The apoptosis in the islet tissue was detected by TUNEL staining. The protein levels of caspase-3, Bcl-2 and Bax were determined by Western blot. The level of miR-375 in the islet tissue was detected by qPCR. Forin vitro study, the MIN-6 cells were cultured and divided into control group (incubated with equivalent amount of solvent), miR-375 mimic group and miR-375 mimic+ liraglutide group. The cell viability was examined by MTT assay. The protein levels of caspase-3, Bcl-2 and Bax were detected by Western blot. RESULTS: In thein vitro study, compared with control group, the levels of BW, FBG, FINS, TC, TG and LDL-C were decreased significantly in liraglutide group. The islet apoptosis was reduced by the administration of liraglutide. The expression of Bcl-2 was up-regulated significantly, while the protein levels of caspase-3 and Bax were down-regulated significantly in liraglutide group. The level of miR-375 was decreased significantly. In the in vitro study, the cell viability was decreased in miR-375 mimic group and increased in miR-375 mimic+liraglutide group. Moreover, the expression of Bcl-2 was decreased and the protein levels of caspase-3 and Bax were increased with the incubation of miR-375 mimic, while the expression of Bcl-2 was increased and the protein levels of caspase-3 and Bax were decreased with the co-incubation of miR-375 mimic and liraglutide. CONCLUSION: Liraglutide attenuates islet apotosis, and the mechanism may be associated with its effects of reducing the elevated level of miR-375 in islet tissues.  相似文献   

18.
ATM: To investigate the effect of oxymatrine (OXY) on high fat-induced insulin resistance in mice, and to investigate the mechanism. METHODS: ApoE-/-mice with high-fat diet for 16 weeks were divided into insulin resistance group, and OXY groups at concentrations of 25, 50 and 100 mg/kg. C57BL/6J mice served as normal control group. The mice in OXY groups were gavaged with OXY for 8 weeks. Glucose tolerance test in the mice was performed. Fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), fatty acid (FFA) and fasting insulin (FINS) in the plasma were measured. The mRNA expression of insulin receptor (INSR), insulin receptor substrate-2 (IRS-2), glucose transporter 2 (GLUT2) in the liver tissues was examined by RT-qPCR. The protein levels of GLUT2, INSR, IRS-2, p-INSR, p-IRS-2, PI3K, p-PI3K, serine/threonine protein kinase (AKT) and p-AKT were examined by Western blot.RESULTS: OXY reduced the levels of FBG, TC, TG, FFA and FINS, and attenuated insulin resistance. Compared with insulin resistance group, the mRNA expression of INSR, IRS-2 and GLUT2 significantly increased in OXY groups (P<0.05). The protein levels of p-INSR/INSR, p-IRS-2/IRS-2, p-PI3K/PI3K, p-AKT/AKT and GLUT2 also increased in OXY groups (P<0.05).CONCLUSION: OXY ameliorates high fat-induced insulin resistance in mice via PI3K/AKT pathway.  相似文献   

19.
AIM: To clarify the relationship between expression of leukocyte iNOS-mRNA and pancreatic islet function in the diabetic rats induced by streptozocin (STZ). METHODS: Wistar rats were randomly divided into the control group (n=10) and the diabetic group (n=15). Expression of iNOS-mRNA in the peripheral blood leukocyte, liver and lung were detected with in situ hybridization and the blood sugar and insulin were also measured. RESULTS: It showed that the blood glucose content increased from (8.95±1.80) to (22.84±4.90) mmol·L-1, however, the plasma insulin content decreased from (81.76±2.12) to (58.92±18.20) mU·L-1 at the third day after the β cell was disfunctioned by STZ injection. No expression of leukocyte iNOS-mRNA in normal rat was detected. The percent rate of positive cells were significantly increased in the rats with diabetes. CONCLUSION: The expression of leukocyte iNOS-mRNA is positively related to the damage of β cells caused by STZ.  相似文献   

20.
AIM: To observe the effect of Tangshenfang (TS) on the liver protection and the levels of silent information regulator 1 (SIRT1) and peroxisom proliferator-activated receptor γ coactivator-1α (PGC-1α) in the liver tissue. METHODS: The rat model of diabetes mellitus (DM) was established by intravenous injection of streptozotocin (STZ;30 mg/kg) after having the high fat/high glucose diets for 1 month. The diabetic rats were randomly divided into DM group, DM with high-dose TS (TSHi) group, medium-dose TS (TSMed) group and low-dose TS (TSLow)group. The normal rats were served as control group. There were 8 rats in each group. After treatment with TS for 12 weeks, the serum biochemical indices including fasting blood glucose (FBG), triglyceride (TG), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were tested. Fasting insulin (FINS) was also detected by radioimmunoassay, and homeostatic model assessment for insulin resistance (HOMA-IR) was calculated. The serum levels of tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1) were measured by ELISA. The activity of SOD and content of MDA in the liver tissues were measured by the methods of hydroxylamine and thiobarbituric acid. The liver pathological changes were observed under light microscope with HE and Masson staining. The protein expression of SIRT1and PGC-1α in the liver tissues was determined by Western blot. RESULTS: In DM group, serum FBG, TG, ALT, AST, FINS, HOMA-IR, TNF-α and IL-1 were obviously increased compared with the control group (P<0.01). The fatty changes, local necrosis, inflammation and fibrosis in the liver tissues were observed. The content of MDA in liver increased, while the activity of SOD decreased markedly. The protein expression of SIRT1 and PGC-1α was decreased (P<0.05). In TS treatment groups, all these changes in DM rats were markedly reversed by TS, and the protein expression of SIRT1 and PGC-1α in the liver tissues was markedly increased. CONCLUSION: TS may protect the rats from diabetic liver injury by increasing the expression of SIRT1 and PGC-1α, and thereby improving insulin resistance and oxidative stress.  相似文献   

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