Diabetic cardiomyopathy is characterized by impaired ventricular contraction and 
altered function of insulin-like growth factor I (IGF-I), a key factor for 
cardiac growth and function. Endogenous IGF-I has been shown to alleviate 
diabetic cardiomyopathy. This study was designed to evaluate exogenous IGF-I 
treatment on the development of diabetic cardiomyopathy. Adult rats were divided 
into four groups: control, control + IGF-I, diabetic, and diabetic + IGF-I. 
Streptozotocin (STZ; 55 mg/kg) was used to induce experimental diabetes 
immediately followed by a 7-wk IGF-I (3 mg. kg(-1). day(-1) ip) treatment. 
Mechanical properties were assessed in ventricular myocytes including peak 
shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR(90)) and 
maximal velocities of shortening/relengthening (+/-dL/dt). Intracellular Ca(2+) 
transients were evaluated as Ca(2+)-induced Ca(2+) release and Ca(2+) clearing 
constant. Levels of sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA), 
phospholamban (PLB), and glucose transporter (GLUT4) were assessed by Western 
blot. STZ caused significant weight loss and elevated blood glucose, 
demonstrating the diabetic status. The diabetic state is associated with reduced 
serum IGF-I levels, which were restored by IGF-I treatment. Diabetic myocytes 
showed reduced PS and +/-dL/dt as well as prolonged TPS, TR(90), and 
intracellular Ca(2+) clearing compared with control. IGF-I treatment prevented 
the diabetes-induced abnormalities in PS, +/-dL/dt, TR(90), and Ca(2+) clearing 
but not TPS. The levels of SERCA and GLUT4, but not PLB, were significantly 
reduced in diabetic hearts compared with controls. IGF-I treatment restored the 
diabetes-induced decline in SERCA, whereas it had no effect on GLUT4 and PLB 
levels. These results suggest that exogenous IGF-I treatment may ameliorate 
contractile disturbances in cardiomyocytes from diabetic animals and could 
provide therapeutic potential in the treatment of diabetic cardiomyopathy.