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Objective To investigate the effect of electroacupuncture on hypothalamic insulin receptor substrate 1 (IRS-1) in a rat model of type 2 diabetes mellitus (T2DM). Methods Sixty Wistar rats were randomized to a normal group (15 rats) and an observation group (45 rats). In the observation group, a rat model of T2DM was made by high-energy diet induction. After the model was successfully made 8 weeks later, the observation group was randomized to model making, treatment and blocker groups, 15 rats each. The treatment group received electroacupuncture and the blocker group, electroacupuncture plus intraventricular perfusion of phosphatidylinositol 3-hydroxyl kinase (PI3K) blocker. After 8 weeks of treatment, fasting plasma glucose (FPG) was measured using a glucometer, fasting insulin (Fins) was determined by ELISA, insulin resistance index (IRI) was calculated and IRS-1 expression was examined by SABC immunohistochemistry assay in every group of rats. Results FPG and Fins increased significantly (both P<0.01) and IRI and IRS-1 expression decreased significantly (P<0.01) in the model making group compared with the normal group. FPG and Fins decreased significantly (both P<0.01) and IRI and IRS-1 expression increased significantly (P<0.01) in the treatment group compared with the model making group. FPG and Fins decreased significantly (P<0.05, P<0.01) and IRI and IRS-1 expression increased significantly (P<0.01) in the treatment group compared with the blocker group. Conclusion Electroacupuncture can improve FPG, Fins and insulin sensitivity by regulating hypothalamic IRS-1 expression in T2DM rats.
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Insulins maintain blood glucose homeostasis in the body by stimulating glucose uptake into muscle and adipose tissues through glucose transporter type 4 (GLUT4)translocation. Recent studies have showed that Rab proteins,as a key regulatory factor for the translocation of GLUT4 to the cell membrane,participate in the formation,translocation and fusion of GLUT4 vesicles. This paper describes several types Rab proteins and the Rab GTPase activating protein,protein kinase B substrate of 160 kU(AS160)in terms of regulatory mechanisms for GLUT4 translocation. Studies on the translocation mechanism by which GLUT4 is regulated by Rabs aim to explain the mechanism of insulin resistance in type 2 diabetes,and provide a new approach to diabetes.
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Objective To observe the effects of high-fat feeding on growth and the expression of insulin-like growth factor 1 (IGF-1),insulin receptor substrate 1 (IRS-1) in adolescent rats'liver with non-alcoholic fatty liver disease,and to elucidate the relationship between growth failure in adolescent rats with non-alcoholic fatty liver disease and IGF-1,IRS-1 turbulence.Methods Thirty-six Sprague-Dawley (SD) young rats of 21 days were randomly divided into normal control group(NC group,n =18) and high-fat feeding group(HF group,n =18).Non-alcoholic fatty liver disease(NAFLD) model was induced by feeding the SD rats with high-fat food.Immunohistochemistry was applied to detect the expression levels of IGF-1 and IRS-1 in liver tissue.The expressions of mRNA of IGF-1 and IRS-1 were measured by RT-PCR.Results Compared with NC group,the serum alanine amino transferase (ALT),total cholesterol (TC),triglyceride (TG) of HF group in the 6th,8 th,12th week were gradually increased.The serum ALT [(194.67 ± 11.15) U/L],TC [(1.81 ± 0.09) mmol/L],TG [(0.34 ± 0.05) mmol/L] contents of HF group at 8th week were higher than those at 6th week [(166.00 ± 22.01) U/L,(1.52 ± 0.22) mmol/L,(0.41 ±0.12) mmol/L,respectively],and the serum ALT[(213.0 ±27.67) U/L],TC[(2.15 ±0.37) mmol/L],TG[(0.38 ±0.15)mmol/L] contents of the 12th week were significantly increased compared with 6th week and 8th week.The constitution and body length of the HF group were lower than those of the normal control group.With time extended,the liver tissue steatosis,inflammation,the balloon like change of the liver tissue pathology of HF group in 6,8,12th week gradually increased.Immunohistochemistry results showed that HF group IRS-1 [(1.46 ± 0.23),(0.74 ± 0.17),(0.85 ± 0.31)],IGF-1 [(0.92 ± 0.02),(0.83 ± 0.02),(0.77 ± 0.03)] expression gradually decreased,the difference was statistically significant(F =36.024,P ＜ 0.05).IGF-1 and IRS-1 mRNA expressions in HF group were consistent.Conclusion The liver tissue IGF-1 and IRS-1 are correlated with the weight and body length.The growth failure of young rats induced by high-fat feeding may be related to the decreased expression of IGF-1 and IRS-1.
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Nos últimos anos, tem havido uma redução acentuada nos índices de cárie dentária em diversas regiões do mundo, fato que tem sido atribuído ao uso de produtos fluoretados, como o dentifrício. Simultaneamente, nota-se a ocorrência do aumento da prevalência de fluorose dentária. O NaF ocasiona inibição da glicólise, diminuição da secreção de insulina e hiperglicemia. Muitas destas respostas sugerem que o NaF pode ocasionar resistência à insulina. Sabendo-se que o fluoreto pode alterar o metabolismo de carboidratos, tornou-se fundamental caracterizar o efeito do NaF sobre: 1) o grau de fosforilação em serina do IRS-1, em tecidos responsivos à insulina; 2) concentração plasmática de colesterol, triglicérides e TNF-α. Para tanto, foram utilizados ratos Wistar (1 mês de idade) castrados. Após 30 dias da castração, os animais foram divididos aleatoriamente em dois grupos: 1) grupo controle (CN), o qual foi submetido ao tratamento sem NaF, mas com uma solução de NaCl (9,54 mg/kg p.c.) que contém a mesma quantidade de sódio em relação à do grupo fluoreto de sódio; 2) grupo NaF (FN) que foi submetido ao tratamento com NaF (4,0 mg de flúor/kg p.c.) na água de beber e na ração durante 42 dias. Após 6 semanas, foi realizada a avaliação da concentração plasmática de TNF-α e a quantificação do grau de fosforilação em serina de IRS-1, após estímulo insulínico, em tecido muscular gastrocnêmio (G), tecido hepático (TH) e em tecido adiposo branco periepididimal (TAB). Também foi realizada a avaliação da concentração plasmática de colesterol e triglicérides. O tratamento crônico com NaF promoveu: 1) aumento significativo, após estímulo insulínico, no grau de fosforilação em serina do substrato do receptor de insulina (IRS-1) no tecido adiposo branco; 2) nenhuma alteração, após estímulo insulínico, no grau de fosforilação em serina do substrato do receptor de insulina (IRS-1) nos tecidos muscular e hepático; 3) aumento na concentração plasmática de TNF-α, triglicérides, colesterol...
Over the last years, there has been a significant reduction in the incidence of dental caries in several regions of the world. This has been attributed to the use of fluoridated products, such as toothpaste. Simultaneously, there has been an increase in the prevalence of dental fluorosis. NaF causes glycolysis inhibition, decrease on insulin secretion and hyperglycemia. These responses suggest that NaF can cause insulin resistance. Knowing that F can interfere with carbohydrate metabolism, we felt it was important and fundamental to undertake a study to examine the chronic effect of NaF on: 1) IRS-1 serine phosphorylation in insulin responsive tissues; 2) plasmatic concentration of cholesterol, triglycerides and TNF alpha. For this study, castrated Wistar male rats (1 month of age) were used. Thirty days after castration, the animals were randomly divided in two groups: 1) control group (CN) which was subjected to treatment without NaF, but with a solution of NaCl (9.54 mg / kg bw) which contains the same amount of sodium in relation to the group NaF; 2) group NaF (FN) that was submitted to treatment with NaF administered in the drinking water and F contained in food pellets (F total inferred: 4.0 mg F / Kg bw / day in the form of NaF) during 42 days. After 6 weeks, the evaluation of plasmatic concentration of TNF-α and quantification of IRS-1 serine phosphorylation status after insulin stimulus in muscle, liver and white adipose tissue were performed. The plasmatic concentration of cholesterol and triglycerides also were evaluated. The chronic treatment with NaF promoted: 1) increase in the IRS-1 serine phosphorylation status after insulin stimulus in the white adipose tissue; 2) no alteration in the IRS-1 serine phosphorylation status after insulin stimulus in the liver and muscle; 3) increase in the plasmatic concentration of TNF-α, triglycerides, total cholesterol and VLDL-cholesterol; 4) no alteration in the plasmatic concentration of HDL cholesterol..
Assuntos
Animais , Ratos , Diabetes Mellitus , Intoxicação por Flúor , Flúor , Insulina , Proteínas Substratos do Receptor de Insulina , Ratos WistarRESUMO
Nos últimos anos, tem havido uma redução acentuada nos índices de cárie dentária em diversas regiões do mundo, fato que tem sido atribuído ao uso de produtos fluoretados, como o dentifrício. Simultaneamente, nota-se a ocorrência do aumento da prevalência de fluorose dentária. O NaF ocasiona inibição da glicólise, diminuição da secreção de insulina e hiperglicemia. Muitas destas respostas sugerem que o NaF pode ocasionar resistência à insulina. Sabendo-se que o fluoreto pode alterar o metabolismo de carboidratos, tornou-se fundamental caracterizar o efeito do NaF sobre: 1) o grau de fosforilação em serina do IRS-1, em tecidos responsivos à insulina; 2) concentração plasmática de colesterol, triglicérides e TNF-α. Para tanto, foram utilizados ratos Wistar (1 mês de idade) castrados. Após 30 dias da castração, os animais foram divididos aleatoriamente em dois grupos: 1) grupo controle (CN), o qual foi submetido ao tratamento sem NaF, mas com uma solução de NaCl (9,54 mg/kg p.c.) que contém a mesma quantidade de sódio em relação à do grupo fluoreto de sódio; 2) grupo NaF (FN) que foi submetido ao tratamento com NaF (4,0 mg de flúor/kg p.c.) na água de beber e na ração durante 42 dias. Após 6 semanas, foi realizada a avaliação da concentração plasmática de TNF-α e a quantificação do grau de fosforilação em serina de IRS-1, após estímulo insulínico, em tecido muscular gastrocnêmio (G), tecido hepático (TH) e em tecido adiposo branco periepididimal (TAB). Também foi realizada a avaliação da concentração plasmática de colesterol e triglicérides. O tratamento crônico com NaF promoveu: 1) aumento significativo, após estímulo insulínico, no grau de fosforilação em serina do substrato do receptor de insulina (IRS-1) no tecido adiposo branco; 2) nenhuma alteração, após estímulo insulínico, no grau de fosforilação em serina do substrato do receptor de insulina (IRS-1) nos tecidos muscular e hepático; 3) aumento na concentração plasmática de TNF-α, triglicérides, colesterol...
Over the last years, there has been a significant reduction in the incidence of dental caries in several regions of the world. This has been attributed to the use of fluoridated products, such as toothpaste. Simultaneously, there has been an increase in the prevalence of dental fluorosis. NaF causes glycolysis inhibition, decrease on insulin secretion and hyperglycemia. These responses suggest that NaF can cause insulin resistance. Knowing that F can interfere with carbohydrate metabolism, we felt it was important and fundamental to undertake a study to examine the chronic effect of NaF on: 1) IRS-1 serine phosphorylation in insulin responsive tissues; 2) plasmatic concentration of cholesterol, triglycerides and TNF alpha. For this study, castrated Wistar male rats (1 month of age) were used. Thirty days after castration, the animals were randomly divided in two groups: 1) control group (CN) which was subjected to treatment without NaF, but with a solution of NaCl (9.54 mg / kg bw) which contains the same amount of sodium in relation to the group NaF; 2) group NaF (FN) that was submitted to treatment with NaF administered in the drinking water and F contained in food pellets (F total inferred: 4.0 mg F / Kg bw / day in the form of NaF) during 42 days. After 6 weeks, the evaluation of plasmatic concentration of TNF-α and quantification of IRS-1 serine phosphorylation status after insulin stimulus in muscle, liver and white adipose tissue were performed. The plasmatic concentration of cholesterol and triglycerides also were evaluated. The chronic treatment with NaF promoted: 1) increase in the IRS-1 serine phosphorylation status after insulin stimulus in the white adipose tissue; 2) no alteration in the IRS-1 serine phosphorylation status after insulin stimulus in the liver and muscle; 3) increase in the plasmatic concentration of TNF-α, triglycerides, total cholesterol and VLDL-cholesterol; 4) no alteration in the plasmatic concentration of HDL cholesterol..
Assuntos
Animais , Ratos , Diabetes Mellitus , Intoxicação por Flúor , Flúor , Insulina , Proteínas Substratos do Receptor de Insulina , Ratos WistarRESUMO
A doença periodontal é considerada, pela Organização Mundial da Saúde, como a sexta complicação clássica do diabético. O diabetes pode influenciar a prevalência, severidade e progressão da periodontite. A literatura mostra uma associação bidirecional entre periodontite e Diabetes mellitus (DM). DM afeta negativamente a condição periodontal e a periodontite afeta negativamente o controle glicêmico, aumentando, assim, o risco de complicações no paciente diabético. No entanto, ainda não há estudos que demonstrem que um processo inflamatório local, como a doença periodontal per si, possa induzir alterações nas etapas iniciais no sinal insulínico em indivíduos não diabéticos. Portanto, o objetivo deste estudo foi avaliar se a doença periodontal é capaz de causar alteração na etapa inicial do sinal insulínico e na sensibilidade à insulina em ratos não diabéticos. Para tanto, foram utilizados ratos Wistar (02 meses de idade) e os animais foram divididos em dois grupos: ratos com doença periodontal (DP) induzida por ligadura e ratos-controle (CN). Após 28 dias da colocação da ligadura, realizaram-se os experimentos: 1) coleta de sangue (n=10) e obtenção de plasma para análise das concentrações de glicose, frutosamina, colesterol total, colesterol HDL (HDL-C), triglicérides, TNF-α, IL-6 e resistina; 2) teste de tolerância à insulina (ITT) para a avaliação da sensibilidade à insulina (n=7); 3) avaliação tanto do grau de fosforilação em tirosina da pp185 (IRS-1/IRS-2) e em serina do IRS-1 como dos conteúdos de IRβ e de IRS-1 em tecidos adiposo branco periepididimal, muscular esquelético e hepático. A partir dos resultados pode-se observar que os ratos com DP apresentaram: 1) redução na sensibilidade à insulina (p<0.05); 2) nenhuma alteração nas concentrações plasmáticas de glicose, frutosamina, colesterol total, HDL-C, triglicérides; 3) aumento nas concentrações plasmáticas de TNF-α, mas nenhuma alteração nas concentrações de IL-6 e resistina; 4) diminuição (p<0.05)...
Periodontal disease (PD) is considered by the World Health Organization as the sixth classic complication of diabetes. Diabetes may influence the prevalence, severity and progression of periodontitis. The literature shows a bidirectional association between periodontitis and Diabetes mellitus (DM). DM negatively affects periodontal status and periodontal disease, in addition to adversely affecting glycemic control, increasing the risk of complications in diabetic patients. However, there are no studies showing that local inflammatory events, such as periodontal disease, per si, can induce changes in early steps of insulin signaling in non-diabetic individuals. Therefore, the purpose of this study was to determine whether periodontal disease can cause changes in the initial phase of insulin signaling and in insulin sensitivity in non-diabetic rats. For this purpose, Wistar rats (two-month-old) were used in the present study. The animals were divided into two groups: 1) group with ligature-induced periodontal disease (PD); 2) control group (CN). Twenty eight days after ligature placement, experiments were carried out: 1) blood collection (n = 10) obtaining plasma for glucose, fructosamine, total cholesterol, HDL cholesterol (HDL-C), triglycerides, TNF-α, IL-6 and resistin analyses; 2) insulin tolerance test (ITT) for evaluating insulin sensitivity (n = 7); 3) assessment of both pp185 (IRS-1 / IRS-2) tyrosine phosphorylation and IRS-1 serine phosphorylation status, and IRβ and IRS-1 content in periepididymal white adipose tissue, skeletal muscle and liver. Observation of results in rats with DP showed: 1) reduction in insulin sensitivity (p <0.05); 2) no change in glucose, fructosamine, total cholesterol, HDL-C and triglycerides plasmatic concentrations; 3) increase in TNF-α plasmatic concentration, but no changes in IL-6 and resistin plasma levels; 4) decrease in (p <0.05) pp185 (IRS-1/IRS-2) tyrosine phosphorylation status after insulin stimulation in white
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Animais , Ratos , Inflamação , Proteínas Substratos do Receptor de Insulina , Resistência à Insulina , Periodontite , Ratos WistarRESUMO
ObjectiveTo investigate the effect of soluble β-amyloid protein (Aβ) oligomers on the expression levels of insulin signaling transduction cascades-associated proteins including insulin receptor ( InsR),insulin receptor substrate-Ⅰ( IRS-Ⅰ) and protein kinase B (PKB) of rat hippocampal neurons,and the pathogenesis of Alzheimer's disease (AD) in depth.MethodsSoluble Aβ oligomers (5 μl) were injected into the lateral ventriculus of the AD group by a microinjector under the stereotaxic apparatus.Normal saline solution ( NS,5 μl) was injected into the NS group in the same way,and the control group received the puncture without injection. It was repeated after 1 week and the behavior of all rats was evaluatedbyY-mazetestafter2weeks.Thenhippocampuswasremovedandunderwent immunohistochemical staining to detect the expression of proteins associated.ResultsCompared with the other groups,learning and memory ability of the Aβ-treated rats were impaired.To be specific,the times of learning were increased and the times of memory were decreased. However,there was no significant difference between the NS group and the control group.Besides,the expression levels of InsR,IRS-Ⅰ,and PKB were decreased in AD group showing that a mean optical density of staining on these proteins ( InsR:0.12 ± 0.0l ; IRS-Ⅰ:0.14 ± 0.02; PKB:0.12 ± 0.03 ) was reduced in contrast with that in the NS group and the control group.Whereas there was no significant difference between the NS group (0.40 ± 0.02,0.39 ± 0.06,0.38 ± 0.03,mean difference:- 0.13,- 0.13,- 0.17,all P ＜ 0.05 ) and the control group (0.38 ± 0.07,0.35 ± 0.03,0.35 ± 0.06,mean difference:- 0.15,- 0.07,- 0.73,all P ＜ 0.05 ).ConclusionsSoluble Aβ1-42 induced learning and memory disability of the rats.The mechanism might be that Aβ can lead to disorders of the insulin signaling transduction pathway of hippocampal neurons and decrease the expression levels of the proteins in the pathway.