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Objective To investigate the effects of Metformin on serum proprotein convertase subtilisin/kexin type 9(PCSK9)level in patients with type 2 diabetes(T2DM). Methods 48 healthy people with normal glucose tolerance were selected as the controls (NGT group). 93 newly diagnosed T2DM were randomized to Metformin treated group (Met,n= 47 )and Glipizide treated group (Gli,n=46).Serum PCSK9 was measured by ELISA in all participants. After treatment,the changes of serum PCSK9 were observed in Met group and Gli group. Results Serum PCSK9 levels in Met group and Gli group were higher than NGT group(P<0. 01). PCSK9 level was positively correlated with FPG,HbA1 c, HOMA-IR,FIns,TC,LDL-C,TG,hsC-RP,TNF-αand BMI (r= 0. 578,0. 638,0. 556,0. 610,0. 578, 0. 592,0. 589,0. 638,0. 561,0. 552;P<0. 05 or P<0. 01),and negatively correlated with HDL-C(r=-0. 614,P<0. 01). The levels of PCSK9 significantly decreased after treatment with Metformin(P<0. 05). PCSK9 levels had no significant differences before and after treatment with Glipizide. Multiple regression analysis showed that TNF-αand HOMA-IR were independent related factors of PCSK9. Conclusion T2DM patients have high levels of serum PCSK9 which can be decreased by Metformin.
ABSTRACT
Aim To discuss the effects and mechanism of Ganoderma lucidum polysaccharides and metformin on myocardial structure and hemodynamics in type 2 diabetic rats.Methods High fat diet combined with intraperitoneal injection of low dose streptozotocin 30 mg· kg -1 was applied to establish rat model of type 2 diabetes mellitus .The diabetic rats were randomly into normal control group ,diabetes group , ganoderma lucid-um polysaccharides group (600 mg· kg -1 ) , metformin group ( 600 mg · kg -1 ) , combination group ( ganoder-ma lucidum polysaccharides 300 mg · kg -1 +metform-in 300 mg· kg -1 ) .After 12 weeks′treatment,the lev-els of fasting serum glucose were determined and the hemodynamic parameters (LVSP,LVEDP,dp/dtmax,-dp/dtmax ) were determined.Collagen volume fraction ( CVF ) was detected by Van Gieson . Immunohisto-chemical method and Western blot were used to detect myocardial tissue MMP-2 protein expression .Results The fasting blood glucose was significantly decreased in the combined treatment group .Combined medication could significantly improve hemodynamic parameters in diabetic rats: reduced LVEP and raised LVEDP , dp/dtmax and -dp/dtmax .CVF was significantly decreased in combination group .The expression of MMP-2 in my-ocardial tissue was significantly inhibited .Conclusions The combination of Ganoderma lucidum polysaccha-ride and metformin can significantly improve the hemo-dynamic parameters in type 2 diabetic rats, and have a preventive effect on diabetic cardiomyopathy . The mechanism may be related to the down regulation of the expression of MMP-2.
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The body is equipped with kinds of transporters which generally exist in liver,kidney,and intestine.Multidrug and toxin extrusion proteins(MATEs;SLC47A)are predominantly expressed in the brush-border membrane of proximal tubule epi-thelial cells in the kidney and the canalicular membrane of hepa-tocytes.Functionally,MATEs act as efflux transporters for or-ganic compounds.The article discusses type,structure,poly-morphism and function of MATE1and MATE2-K,and also dis-cusses the effect of single nucleotide polymorphisms (SNPs)in the SLC47A1 gene and SLC47A2 on the pharmacokinetics and pharmacodynamics of metformin and platinum-based chemothera-peutic agents.
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Aim To investigate the effects and mecha of ganoderma lucidum polysaccharides and metformin on pathological changes of thoracic aorta in diabetic ratsandthemechanisms.Methods SDratswerefed with high fat diet for 4 weeks and injected with strepto-zotocin ( 30 mg · kg-1 ) to replicate type 2 diabetic model. The diabetic rats were randomly into diabetes group, ganoderma lucidum polysaccharides group ( 600 mg·kg-1 ) ,metformin group(600 mg·kg-1 ) ,combi-nation group ( ganoderma lucidum polysaccharides 300 mg· kg-1 + metformin 300 mg · kg-1 ) and normal control group. After 12 weeksˊ treatment, the levels of fasting serum glucose, the activity of catalase(CAT), glutathione peroxidase ( GSH-Px ) , total cholesterol (TC)and triglyceride(TG) in serum were detected. Pathological changes of thoracic aorta were observed by HE staining. Immunohistochemy and Western blot were used to detect thoracic aorta VEGF protein expression. Results Combination group could lower fasting serum glucose and blood fat significantly, meanwhile the ac-tivity of CAT and GSH-Px in serum was improved. The expression of VEGF in thoracic aorta was repressed. The result of HE staining suggested that the lipid de-posits in aortic endothelium in combination group were lessthanthoseinthemodelgroup.Conclusions Ga-noderma lucidum polysaccharides combined with met-formin has an obvious prevention on pathological chan-ges of thoracic aorta in diabetic rats. The possible mechanism may be related to repressing oxidative stress of thoracic aorta, regulating the dyslipidemia, and the down regulation of the expression of VEGF in thoracic aorta.
ABSTRACT
Aim To study the effects of ganoderma lu-cidum polysaccharides and metformin on myocardial fi-brosis of type 2 diabetic rats and its mechanism. Methods SD rats were fed with high fat diet for 4 weeks, and then were injected with streptozotocin (30mg·kg-1 ) to replicate type 2 diabetic model. The diabetic rats were randomized into normal control group,diabetes group, ganoderma lucidum polysaccha-rides group ( 600 mg · kg-1 ) , metformin group ( 600 mg·kg-1 ) , and combination group( ganoderma lucid-um polysaccharides 300 mg·kg-1 +metformin 300 mg ·kg-1 ) . After 12 weeks’ treatment,the levels of fast-ing serum glucose were determined and the extent of myocardial fibrosis was observed by Picro-sirius red staining. The contents of AGEs in serum were deter-mined by fluorescence spectrophotometer. The activities of CAT and GSH-Px in myocardium were detected. Im-munohistochemical method and Western blot were used to detect myocardial tissue AGEs and CTGF protein ex-pression. Results Combination group could repress patho-proceeding of myocardial fibrosis efficiently, im-prove the activity of CAT and GSH-Px in myocardium and lower the concentration of AGEs in serum, as well as reduce the expression of AGEs and CTGF in myo-cardium. Conclusions Ganoderma lucidum polysac-charides and metformin could prevent myocardial fibro-sis. The possible mechanism may be related to repress-ing oxidative stress of myocardium, lowering serum AGEs and down regulating AGEs and CTGF of myocar-dium.