title: Suppression of connective tissue growth factor mediates the renoprotective effect of Sitagliptin rather than Pioglitazone in type 2 diabetes mellitus.
abstract: OBJECTIVE
  Diabetic nephropathy (DN) is a leading cause of end-stage renal disease, and thus, the ability of antidiabetic drugs to ameliorate renal microvascular disease may be as important as their ability to control blood glucose. Therefore, we investigated the reno-protective effect of the antidiabetic drugs, Sitagliptin and Pioglitazone, versus combined Metformin/Enalapril in a rat model of type 2 diabetes.
  
  
  METHODS
  Male Wistar rats were randomly assigned to be either normal control or diabetic. Induction of type 2 diabetes was done by intraperitoneal injection of\ low dose streptozotocin (35mg/kg) on top of 2 weeks of high fat diet. Hyperglycemic animals were divided into 4 groups: untreated diabetic, Sitagliptin (10mg/kg), Pioglitazone (10mg/kg) and Metformin/Enalapril (500, 10mg/kg, respectively) treated. After 6 weeks, fasting blood glucose, plasma insulin, β-cell function, insulin resistance, serum lipids, urea & creatinine, albuminurea, kidney weight, renal oxidative stress, plasma connective tissue growth factor (CTGF) and renal histopathology were assessed.
  
  
  RESULTS
  Sitagliptin decreased microalbuminurea, urea & creatinine, renal tropism, oxidative stress and CTGF to levels similar to Metformin/Enalapril group. It also preserved near normal renal histology. Although Pioglitazone treatment reduced urea, creatinine, renal tropism and oxidative stress, it did not improve renal pathological changes or significantly alter CTCF.
  
  
  CONCLUSIONS
  Early Sitagliptin treatment in type 2 diabetes can equally ameliorate renal functions and structural changes as combined Metformin/Enalapril. Moreover Sitagliptin is a better renoprotective than Pioglitazone, probably due to its suppressor effect on CTGF, a key factor mediating diabetic renal injury.
authors.affiliation: Department of Clinical Pharmacology, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
authors.forename: Samia M
authors.initials: SM
authors.lastname: Ali
authors.affiliation: Department of Histology and cell Biology, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
authors.forename: Hoda
authors.initials: H
authors.lastname: Khalifa
authors.affiliation: Department of Clinical Pharmacology, Faculty of Medicine, Alexandria University, Alexandria, Egypt. Electronic address: dalia.kashishy@alexmed.edu.eg.
authors.forename: Dalia K
authors.initials: DK
authors.lastname: Mostafa
authors.affiliation: Department of Clinical Pharmacology, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
authors.forename: Amal
authors.initials: A
authors.lastname: El Sharkawy
mesh_terms: D000818:Animals; D055513:Connective Tissue Growth Factor / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D000077205:Pioglitazone; D051381:Rats; D017208:Rats, Wistar; D000068900:Sitagliptin Phosphate / Q000494:pharmacology*; D045162:Thiazolidinediones / Q000494:pharmacology*
chemical_list: D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D055513:Connective Tissue Growth Factor; D000068900:Sitagliptin Phosphate; D000077205:Pioglitazone
keywords: CTGF; Diabetic nephropathy; Enalapril; Metformin; Pioglitazone; Sitagliptin