ABSTRACT
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.
ABSTRACT
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.