Advanced glycation end products(AGEs), which are macromolecular material such as proteins, lipids, and nucleic acids free amino and reducing sugar on the reaction of aldehyde group under the condition of the enzyme, g...Advanced glycation end products(AGEs), which are macromolecular material such as proteins, lipids, and nucleic acids free amino and reducing sugar on the reaction of aldehyde group under the condition of the enzyme, generate the stable compounds. AGEs formation is enhanced in diabetes and is associated with the development of diabetic complications. AGEs, as an important marker of chronic complications of diabetes mellitus, plays an important role in the development and progression of diabetic nephropathy. In the current review, we discuss mechanisms and the role of AGEs in diabetic nephropathy.展开更多
To study the relationship between advanced glycosylation end products (AGE) and protein kinase C (PKC), and their effects on renal alteration in diabetic rats Methods Insulin or aminoguanidine was administered to di...To study the relationship between advanced glycosylation end products (AGE) and protein kinase C (PKC), and their effects on renal alteration in diabetic rats Methods Insulin or aminoguanidine was administered to diabetic rats Blood glucose, hemoglobin A 1C (HbA 1C ), glomerular tissue extracts AGE (GTE AGE), PKC, glomerular basement membrane thickness (GBMT) and urine protein/creatinine (Pr/Cr) ratio in diabetic rats were measured and analysed Results Levels of blood glucose, HbA 1C and AGE, PKC activity, the Pr/Cr ratio and GBMT were all significantly increased ( P values all less than 0 01) in diabetic rats Insulin could decrease the formation of HbA 1C and AGE, and improve PKC activity Aminoguanidine had no influence on PKC activity ( P >0 05) although it decreased the formation of AGE Both drugs could delay the increase of urine Pr/Cr ratio and GBMT ( P <0 05 or P <0 01) Conclusions Chronic hyperglycemia may lead to an increase of PKC activity HbA 1C and AGE may not directly contribute to alterations of PKC activity, but the increase of PKC activity could promote the action of AGE on GBM thickening It is important to inhibit the formation of AGE and reduce the PKC activity so as to prevent or delay the development of diabetic nephropathy展开更多
Erectile dysfunction （ED） is a major complication of diabetes mellitus. Icariin has been shown to enhance erectile function through its bioactive form, icarisid Ih This study investigates the effects of icarisid Ⅱ ...Erectile dysfunction （ED） is a major complication of diabetes mellitus. Icariin has been shown to enhance erectile function through its bioactive form, icarisid Ih This study investigates the effects of icarisid Ⅱ on diabetic rats with ED and its potential mechanism viathe assessment of advanced glycosylation end products （AGEs）, autophagy, mTOR and the NO-cGMP pathway. Icarisid Ⅱ was extracted from icariin by an enzymatic method. In the control and diabetic ED groups, rats were administered normal saline; in the icarisid Ⅱ group, rats were administered icarisid Ⅱ intragastrically. Erectile function was evaluated by measuring intracavernosal pressure/mean arterial pressure （ICP/MAP）. AGE concentrations, nitric oxide synthase （NOS） activity and cGMP concentration were assessed by enzyme immunoassay. Cell proliferation was analysed using methyl thiazolyl tetrazolium assay and flow cytometry. Autophagosomes were observed by transmission electron microscopy, monodansylcadaverine staining and GFP-LC3 Iocalisation. The expression of NOS isoforms and key proteins in autophagy were examined by western blot. Our results have shown that Icarisid Ⅱ increased ICP/MAP values, the smooth muscle cell （SMC） growth curve, S phase and SMC/collagen fibril （SMC/CF） proportions and decreased Beclin 1 （P〈0.05）. Icarisid Ⅱ significantly increased the proliferative index and p-p70S6K（Thr389） levels and decreased the numbers of autophagosomes and the levels of LC3-11 （P〈0.01）. Icarisid Ⅱ decreased AGE concentrations and increased cGMP concentration, NOS activity （P〈0.05） and cNOS levels （P〈0.01） in the diabetic ED group. Therefore, Icarisid Ⅱ constitutes a promising compound for diabetic ED and might be involved in the upregulation of SMC proliferation and the NO-cGMP pathway and the downregulation of AGEs, autophagy and the mTOR pathway.展开更多
Background Galectin-3 is the most recently identified advanced glycosylation end products （AGEs） binding protein. This study aimed to investigate the effects of AGEs and rosiglitazone on the expression and secretion...Background Galectin-3 is the most recently identified advanced glycosylation end products （AGEs） binding protein. This study aimed to investigate the effects of AGEs and rosiglitazone on the expression and secretion of galectin-3 in cultured human renal mesangial cells （HRMCs）. Methods HRMCs were incubated with different concentrations of AGE-bovine serum albumin （BSA） （0, 50, 100, 200, and 400 mg/L） for different time （0, 24, 36, 48, and 72 hours）, and exposed to AGE-BSA in the presence of different concentrations of rosiglitazone （1, 10, and 100 μmol/L）. The mRNA and protein expression of galectin-3 in HRMCs were analyzed by reverse transcription polymerase chain reaction （RT-PCR） and Western blotting. The culture medium of HRMCs was collected and concentrated, and the content of galectin-3 in the medium was detected by Western blotting. Results Both RT-PCR and Western blotting revealed that AGE-BSA up-regulated the expression of galectin-3 in HRMCs in a concentration- （P 〈0.05） and time-dependent （P 〈0.05） manner compared with the control. Compared with the control, AGE-BSA elevated the content of galectin-3 in the culture medium of HRMCs time- and concentrationdependently （P 〈0.05, respectively）. Both protein and mRNA expression of galectin-3, and its content in the medium of HRMCs exposed to different concentrations of rosiglitazone in the presence of AGE-BSA were increased compared with those of cells exposed to AGE-BSA alone （P 〈0.05）. Rosiglitazone increased the expression and secretion of galectin-3 in a dose-dependent manner （P 〈0.05）. Conclusions AGEs up-regulates the expression and secretion of galectin-3 in HRMCs. Rosiglitazone further enhances the upregulation of galectin-3 in HRMCs induced by AGEs, which suggests that rosiglitazone may play a role of reno-protection via up-regulation of galectin-3.展开更多
文摘Advanced glycation end products(AGEs), which are macromolecular material such as proteins, lipids, and nucleic acids free amino and reducing sugar on the reaction of aldehyde group under the condition of the enzyme, generate the stable compounds. AGEs formation is enhanced in diabetes and is associated with the development of diabetic complications. AGEs, as an important marker of chronic complications of diabetes mellitus, plays an important role in the development and progression of diabetic nephropathy. In the current review, we discuss mechanisms and the role of AGEs in diabetic nephropathy.
文摘To study the relationship between advanced glycosylation end products (AGE) and protein kinase C (PKC), and their effects on renal alteration in diabetic rats Methods Insulin or aminoguanidine was administered to diabetic rats Blood glucose, hemoglobin A 1C (HbA 1C ), glomerular tissue extracts AGE (GTE AGE), PKC, glomerular basement membrane thickness (GBMT) and urine protein/creatinine (Pr/Cr) ratio in diabetic rats were measured and analysed Results Levels of blood glucose, HbA 1C and AGE, PKC activity, the Pr/Cr ratio and GBMT were all significantly increased ( P values all less than 0 01) in diabetic rats Insulin could decrease the formation of HbA 1C and AGE, and improve PKC activity Aminoguanidine had no influence on PKC activity ( P >0 05) although it decreased the formation of AGE Both drugs could delay the increase of urine Pr/Cr ratio and GBMT ( P <0 05 or P <0 01) Conclusions Chronic hyperglycemia may lead to an increase of PKC activity HbA 1C and AGE may not directly contribute to alterations of PKC activity, but the increase of PKC activity could promote the action of AGE on GBM thickening It is important to inhibit the formation of AGE and reduce the PKC activity so as to prevent or delay the development of diabetic nephropathy
文摘Erectile dysfunction （ED） is a major complication of diabetes mellitus. Icariin has been shown to enhance erectile function through its bioactive form, icarisid Ih This study investigates the effects of icarisid Ⅱ on diabetic rats with ED and its potential mechanism viathe assessment of advanced glycosylation end products （AGEs）, autophagy, mTOR and the NO-cGMP pathway. Icarisid Ⅱ was extracted from icariin by an enzymatic method. In the control and diabetic ED groups, rats were administered normal saline; in the icarisid Ⅱ group, rats were administered icarisid Ⅱ intragastrically. Erectile function was evaluated by measuring intracavernosal pressure/mean arterial pressure （ICP/MAP）. AGE concentrations, nitric oxide synthase （NOS） activity and cGMP concentration were assessed by enzyme immunoassay. Cell proliferation was analysed using methyl thiazolyl tetrazolium assay and flow cytometry. Autophagosomes were observed by transmission electron microscopy, monodansylcadaverine staining and GFP-LC3 Iocalisation. The expression of NOS isoforms and key proteins in autophagy were examined by western blot. Our results have shown that Icarisid Ⅱ increased ICP/MAP values, the smooth muscle cell （SMC） growth curve, S phase and SMC/collagen fibril （SMC/CF） proportions and decreased Beclin 1 （P〈0.05）. Icarisid Ⅱ significantly increased the proliferative index and p-p70S6K（Thr389） levels and decreased the numbers of autophagosomes and the levels of LC3-11 （P〈0.01）. Icarisid Ⅱ decreased AGE concentrations and increased cGMP concentration, NOS activity （P〈0.05） and cNOS levels （P〈0.01） in the diabetic ED group. Therefore, Icarisid Ⅱ constitutes a promising compound for diabetic ED and might be involved in the upregulation of SMC proliferation and the NO-cGMP pathway and the downregulation of AGEs, autophagy and the mTOR pathway.
文摘Background Galectin-3 is the most recently identified advanced glycosylation end products （AGEs） binding protein. This study aimed to investigate the effects of AGEs and rosiglitazone on the expression and secretion of galectin-3 in cultured human renal mesangial cells （HRMCs）. Methods HRMCs were incubated with different concentrations of AGE-bovine serum albumin （BSA） （0, 50, 100, 200, and 400 mg/L） for different time （0, 24, 36, 48, and 72 hours）, and exposed to AGE-BSA in the presence of different concentrations of rosiglitazone （1, 10, and 100 μmol/L）. The mRNA and protein expression of galectin-3 in HRMCs were analyzed by reverse transcription polymerase chain reaction （RT-PCR） and Western blotting. The culture medium of HRMCs was collected and concentrated, and the content of galectin-3 in the medium was detected by Western blotting. Results Both RT-PCR and Western blotting revealed that AGE-BSA up-regulated the expression of galectin-3 in HRMCs in a concentration- （P 〈0.05） and time-dependent （P 〈0.05） manner compared with the control. Compared with the control, AGE-BSA elevated the content of galectin-3 in the culture medium of HRMCs time- and concentrationdependently （P 〈0.05, respectively）. Both protein and mRNA expression of galectin-3, and its content in the medium of HRMCs exposed to different concentrations of rosiglitazone in the presence of AGE-BSA were increased compared with those of cells exposed to AGE-BSA alone （P 〈0.05）. Rosiglitazone increased the expression and secretion of galectin-3 in a dose-dependent manner （P 〈0.05）. Conclusions AGEs up-regulates the expression and secretion of galectin-3 in HRMCs. Rosiglitazone further enhances the upregulation of galectin-3 in HRMCs induced by AGEs, which suggests that rosiglitazone may play a role of reno-protection via up-regulation of galectin-3.
