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Objective To observe the effect of supplemental Revolvin D1 (RvD1) on Toll-like receptor 4 (TLR4) in skeletal muscle of type 2 diabetic mice.Methods 35 male C57BL/6 mice were randomly divided into control group (NC group) and high glucose and high fat diet group.After 8 weeks,mice in high glucose and high fat diet group were given intraperitoneal injection of streptozotocin (STZ) 100 mg/ kg.Then they were randomly divided into two groups:Type 2 diabetes group (T2DM group) and type 2 diabetes + RvD1 intervention group (T2DM + RvD1 group).Mice in T2DM group mice were injected with phosphate buffer saline 0.2 ml and T2DM + RvD1 group mice were injected with Revolvin D1 100 ng/day respectively.The levels of fasting blood glucose,serum insulin and inflammatory factors were detected.The mRNA expression level of TLR4 was detected by real-time quantitative polymerase chain reaction (RT-qPCR) method,and the expression of TLR4 protein was detected by Western blot.Results The levels of insulin resistance index,interleukin(IL)-6 and tumor necrosis factor-α (TNF-α) in T2DM group and T2DM + RvD1 group increased (P ＜ 0.05).Compared with the T2DM group,the levels of insulin resistance index,IL-6 and TNF-α in T2DM + RvD1 group decreased (P ＜0.05).The expression of TLR4 protein in T2DM group and T2DM + RvD1 group was higher than that in NC group (P ＜ 0.05).The expression of TLR4 protein in T2DM + RvD1 group,was lower than that in T2DM group (P ＜0.05).The mRNA level of TLR4 in mice was consistent with the above results by RT-qPCR.Conclusions Moderate supplementation of RvD1 can not only decrease the level of inflammatory factors in type 2 diabetic mice,but also reduce the expression of TLR4 and insulin resistance in skeletal muscle of type 2 diabetic mice.
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Objective To investigate sitagliptin and repaglinide could ameliorate endothelial function in newly diagnosed type 2 diabetes patients and to explore its mechanism.Methods A total of 92 newly diagnosed type 2 diabetes patients with glycated hemoglobin A1c (HbA1c) from 6.5％ to 8.5％ was randomly assigned to sitagliptin group(n =46) receiving sitagliptin,and repaglinide group (n =46) receiving repaglinide for 12 weeks.The effect of sitagliptin on vascular endothelial function was measured with endothelium-dependent flow-mediated vasodilation (FMD).FMD,level of serum nitric oxide (NO),plasminogen activator inhibitor-1 (PAI-1) and biochemical variables in the two groups were measured at baseline and 12 weeks after treatment.Results Fasting blood glucose (FBG),postprandial blood glucose (PBG),and HbA1c decreased significantly both in sitagliptin and repaglinide groups after treatment,but the descent more significantly in the repaglinide group than those in the sitagliptin group (P ＜ 0.05).FMD,NO,and homeostasis model assessmentβ (HOMA-[β) were increased,and PAI-1 and homeostasis model assessment-insulin resistance (HOMR-IR) decreased in both two groups of patients (P ＜ 0.05).FMD,NO,and PAI-1 improved more significantly in sitagliptin groups (P ＜ 0.05).With FMD as dependent variables,multiple linear regression analysis showed that NO was a major protection factors of endothelial function,and PAI-1 and mean artery pressure (MAP) were major injury factors of endothelial function.Furthermore,with /FMD as the dependent variable,FMD as the dependent variable,and body mass index (BMI),MAP,HbA1c,HOMA-IR,triglycerides (TG),NO,and PAI-1 as a covariate-linear analysis of covariance showed that improved FMD with NO and PAI-1 were still relevant after treatment with sitagliptin.Conclusions Sitagliptin could improve vascular endothelial function evaluated by FMD better than repaglinide in newly diagnosed type 2 diabetes,the partial mechanism was related to the increase of NO level and the decrease of PAI-1 level,and the effect may be independent of the hypoglycemic effect.
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Objective To investigate sitagliptin and repaglinide could ameliorate endothelial function in newly diagnosed type 2 diabetes patients and to explore its mechanism.Methods A total of 92 newly diagnosed type 2 diabetes patients with glycated hemoglobin A1c (HbA1c) from 6.5％ to 8.5％ was randomly assigned to sitagliptin group(n =46) receiving sitagliptin,and repaglinide group (n =46) receiving repaglinide for 12 weeks.The effect of sitagliptin on vascular endothelial function was measured with endothelium-dependent flow-mediated vasodilation (FMD).FMD,level of serum nitric oxide (NO),plasminogen activator inhibitor-1 (PAI-1) and biochemical variables in the two groups were measured at baseline and 12 weeks after treatment.Results Fasting blood glucose (FBG),postprandial blood glucose (PBG),and HbA1c decreased significantly both in sitagliptin and repaglinide groups after treatment,but the descent more significantly in the repaglinide group than those in the sitagliptin group (P ＜ 0.05).FMD,NO,and homeostasis model assessmentβ (HOMA-[β) were increased,and PAI-1 and homeostasis model assessment-insulin resistance (HOMR-IR) decreased in both two groups of patients (P ＜ 0.05).FMD,NO,and PAI-1 improved more significantly in sitagliptin groups (P ＜ 0.05).With FMD as dependent variables,multiple linear regression analysis showed that NO was a major protection factors of endothelial function,and PAI-1 and mean artery pressure (MAP) were major injury factors of endothelial function.Furthermore,with /FMD as the dependent variable,FMD as the dependent variable,and body mass index (BMI),MAP,HbA1c,HOMA-IR,triglycerides (TG),NO,and PAI-1 as a covariate-linear analysis of covariance showed that improved FMD with NO and PAI-1 were still relevant after treatment with sitagliptin.Conclusions Sitagliptin could improve vascular endothelial function evaluated by FMD better than repaglinide in newly diagnosed type 2 diabetes,the partial mechanism was related to the increase of NO level and the decrease of PAI-1 level,and the effect may be independent of the hypoglycemic effect.
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Objective To investigate the effects of metformin on serum visfatin and the level of visfatin mRNA in visceral adipose tissue of type 2 diabetic rats.Methods Forty Wistar rats were randomly assigned into normal diet group (NC) and diabetic group.The rats in the diabetic group were fed with high glucose and high fat diet, and then injected with streptozotocin (STZ).The diabetic rats were divided into diabetic control (DC), metformin (MET), and insulin-treatment (INS) groups.Eight weeks later, body weight (BW) , visceral adipose tissue weight, and biochemical indicators were assessed.Homeostasis model assessment of insulin resistance (HOMA-IR) and Lee index were calculated.The serum visfatin levels were detected by enzyme-linked immunoassay (EIA), and the visfatin mRNA levels of visceral adipose tissues were detected by real time polymerase chain reaction (PCR).Results Compared to group DC, the visfatin levels of serum and visceral adipose tissue mRNA were lower in INS group, but did not have significant difference (P ＞ 0.05);the visfatin levels of serum and visceral adipose tissue mRNA in MET group were significantly lower (P ＜ 0.01).Conclusions Metformin can reduce the visfatin levels of serum and visceral adipose tissue mRNA, and improve the insulin resistance in type 2 diabetic rats.
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Objective The effects of candesartan,an angiotensin Ⅱ type 1 receptor blocker (ARB) were investigated on advanced glycation end-products accumulation and the receptor for AGE (RAGE) expression in type 2 diabetic KK/Ta mouse kidneys.MethodsKK/Ta mice(n=72)were random divided into three groups(n=24) and it was treated with candesartan [4 mg/(kg·d)] or vehicle from 6 or 12 to 28 weeks of age.BALB/c mice(n=24) treated with vehicle were used as controls.Body weight,blood pressure,blood glucose,urinary microalbumin,urinary creatinine and serum creatinine were measured every four weeks.At 28 weeks,renal expressions of carboxymethyllysine and RAGE were evaluated by immunohistochemistry and/or competitive RT-PCR.Results KK/Ta mice developed high body weight,high blood glucose,and high urinary microalbumin/creatinine ratio in KK/Ta mice at 28 weeks of age,and it was significantly higher than that of BALB/c mice [(427.49±89.37)mg/g vs (9.54±3.25)mg/g,P＜0.01 ].Protein and mRNA expressions of RAGE were upregulated in KK/Ta kidneys with increased immunostaining intensities of carboxymethyllysine.Candesartan treatment has markedly reduced urinary microalbumin/creatinine ratio [Early treatment group (32.18±9.41)mg/g,Late treatment group (53.20±7.26)mg/g,P＜0.01 ].Treatment with candesartan down-regulated the protein and mRNA expressions of RAGE and reduced the accumulation of carboxymethyllysine.There were no significant differences between the two treatment groups (from 6 or 12 weeks).ConclusionsThe results suggest that candesartan,an ARB,reduces advanced glycation end-products accumulation and subsequent albuminuria by down-regulating RAGE expression in type 2 diabetic KK/Ta mouse kidneys.
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Objective To investigate the effect of intensive insulin therapy on long-term remittance of the islet β-cell function in newly diagnosed type 2 diabetic patients. Methods 120 newly diagnosed type 2 diabetic patients were randomly divided into four groups, and intensive insulin therapy was given for 15 days, 30 days, 60 days and 90 days respectively. The islet β-cell function were measured before and 1 or 2 years after treatment, and the differences were compared among each group. Results The plasma glucose was controlled well and the islet β-cell function was significantly improved in each group after treatment. The ratio value of △I30/△G30 in groups of 30 days,60 days and 90 days were higher than group of 15 days[(1.48±0.43 )mmol/L vs (1.25±0.40) mmol/L, t＝2.40,P＜0.05, (1.83±0.37) mmol/L vs (1.25±0.40) mmol/L, t＝2.85,P＜0.01, (1.90±0.41) mmol/L vs (1.25±0.40) mmol/L, t＝2.97,P＜0.01]. The indexes of the islet β-cell secretion function all gradually declined in each group after treatment for 2 years, but still higher than before treatment, the ratio value of △I30/△G30 in groups of 60 days and 90 days were higher than group of 15 days and 30 days[(1.44±0.51)mmol/L vs (0.87±0.47) mmol/L,t＝2.92, P＜0.01, (1.44±0.51)mmol/L vs (1.09±0.55) mmol/L, t＝2.44,P＜0.05, (1.52±0.44) mmol/L vs (0.87±0.47) mmol/L, t＝2.86, P＜0.01, (1.52±0.44) mmol/L vs (1.09±0.55) mmol/L, t＝2.50, P＜0.05], there was no difference between group of 60 days and 90 days. The ratio of remittance in groups of 60 days and 90 days was very high. Conclusions Intensive insulin therapy can significantly improve the islet β-cell function of newly diagnosed type 2 diabetic patients,anddelay the natural process. An appropriate extension of treatment can further prevent the descending rate of islet β-cell function, and easily get the long-term remission.