title: Preservation of heart function in diabetic rats by the combined effects of muscle cell implantation and insulin therapy.
abstract: BACKGROUND
  Diabetic cardiomyopathy is a common cause of heart failure in diabetic patients, but current treatments do not directly improve ventricular function. Cell transplantation can prevent cardiac dilatation after injury, and may also prevent congestive heart failure in diabetic cardiomyopathy.
  
  
  OBJECTIVE
  This study evaluated the functional effects of smooth muscle cells (SMCs) implanted into the myocardium of insulin- and non insulin-treated diabetic rats.
  
  
  METHODS
  Four weeks after streptozotocin infusion, adult Wistar rats were implanted with BrdU-labelled SMCs or culture media (N=12/group). Six rats in each group were also treated with insulin. Echocardiograms were performed at 0, 4 and 8 weeks after streptozotocin injection, and histology and heart function were evaluated at 4 weeks after implantation.
  
  
  RESULTS
  Blood glucose levels decreased after insulin treatment. Among cell-injected rats, histology indicated that those that did not receive insulin retained fewer surviving BrdU+ SMCs, and a smaller volume of myocardial tissue positive for alpha-smooth muscle actin. Cardiac function was preserved in the insulin-treated groups relative to those that did not receive insulin. Among insulin-treated rats, the cell-injected group functioned better than the media-injected group.
  
  
  CONCLUSIONS
  Diabetic cardiomyopathy is partially treatable with insulin; however, a combination of SMC transplantation and insulin treatment produced the best functional result. Cell transplantation may prevent the progression of diabetic cardiomyopathy in patients whose glucose levels are controlled with insulin.
authors.affiliation: Toronto General Research Institute, Division of Cardiovascular Surgery, Toronto, Ontario, Canada.
authors.forename: Byung-Ok
authors.initials: BO
authors.lastname: Kim
authors.forename: Subodh
authors.initials: S
authors.lastname: Verma
authors.forename: Richard D
authors.initials: RD
authors.lastname: Weisel
authors.forename: Shafie
authors.initials: S
authors.lastname: Fazel
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Jia
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Mizuno
authors.forename: Ren-Ke
authors.initials: RK
authors.lastname: Li
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D009202:Cardiomyopathies / Q000209:etiology / Q000628:therapy*; D003131:Combined Modality Therapy / Q000379:methods; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications*; D006085:Graft Survival / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000637:transplantation*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013318:Stroke Volume / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin