Preservation of heart function in diabetic rats by the combined effects of muscle cell implantation and insulin therapy.
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.
Kim
Byung-Ok
BO
Toronto General Research Institute, Division of Cardiovascular Surgery, Toronto, Ontario, Canada.
Verma
Subodh
S
Weisel
Richard D
RD
Fazel
Shafie
S
Jia
Zhi-Qiang
ZQ
Mizuno
Tomohiro
T
Li
Ren-Ke
RK
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
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin