title: Metformin ameliorates podocyte damage by restoring renal tissue nephrin expression in type 2 diabetic rats.
abstract: BACKGROUND
  Previous studies found that metformin provided some renoprotection for diabetic renal damage. In the present study, we evaluated the effects of different doses of metformin on the expression of renal tissue nephrin in type 2 diabetes mellitus (T2DM) model rats and the possible mechanism underlying its protective effect in kidney podocytes.
  
  
  METHODS
  A high-fat diet combined with a low dose of streptozotocin was used to induce T2DM model rats. Diabetic rats were treated with 150, 300, or 500 mg/kg metformin for 8 weeks. At the end of the study, urine and blood samples were collected for measurement of different indices. Light microscopy and transmission electron microscopy were used to identify morphological changes. Renal expression of nephrin protein was assayed by immunohistochemical staining, whereas real-time polymerase chain reaction was used to detect renal nephrin (Nphs1) mRNA expression.
  
  
  RESULTS
  Metformin treatment of T2DM rats produced dose-dependent significant reductions in urinary albumin and nephrin concentrations, glomerular basement membrane thickness (GBMT), and the foot process fusion rate (FPFR) compared with control T2DM model rats, whereas renal expression of nephrin protein and Nphs1 mRNA was dose-dependently increased by metformin treatment.
  
  
  CONCLUSIONS
  Metformin protects kidney podocytes in T2DM model rats by dose-dependently adjusting renal nephrin expression.
authors.affiliation: Department of Endocrinology, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei, China.
authors.forename: Limin
authors.initials: L
authors.lastname: Zhai
authors.affiliation: Department of Endocrinology, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei, China.
authors.forename: Junfei
authors.initials: J
authors.lastname: Gu
authors.affiliation: Department of Endocrinology, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei, China.
authors.forename: Di
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Pathology, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Hu
authors.affiliation: Department of Endocrinology, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei, China.
authors.forename: Shandong
authors.initials: S
authors.lastname: Ye
mesh_terms: D000419:Albuminuria / Q000652:urine; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000209:etiology / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics; D059305:Diet, High-Fat / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D006442:Glycated Hemoglobin / Q000032:analysis; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D008687:Metformin / Q000494:pharmacology*; D046529:Microscopy, Electron, Transmission; D050199:Podocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008565:Membrane Proteins; D008687:Metformin; C113267:nephrin
keywords: diabetic nephropathy; metformin; nephrin; podocytes; 二甲双胍; 糖尿病肾病; 足细胞