Effects of graded insulin therapy on cardiac function in diabetic rats

To determine the effects of graded insulin therapy on cardiac function and biochemistry, rats were made diabetic by streptozotocin (50 mg/kg) and subsequently treated with either 3 U of insulin per day (D3) or 5 U/day (D5) and compared with untreated diabetic rats (D phi) and a nondiabetic control group (C). Blood glucose, water consumption, and heart and body weights in D3 and D5 showed dose-dependent responses between those of D phi and C. Cardiac function was studied at similar heart rates and similar left atrial and aortic pressures in an isolated working heart apparatus. Hearts from D phi showed significant decreases in end-diastolic pressure, peak left ventricular systolic pressure, and positive dP/dt, whereas these values in D3 and D5 were similar to those in C. The isovolumic relaxation period was significantly longer in the D phi group, intermediate between D phi and C in D3, and the same in D5 and C. Ca2+-ATPase activity of myosin and actin-activated Mg2+-ATPase activity was depressed in D phi, partially corrected in D3, and completely corrected in D5. Myosin isoenzyme distribution displayed a shift from the predominant V1 pattern observed in C to a predominant V3 pattern in D phi. Treatment with 3 U of insulin per day partially corrected the isoenzyme abnormality, and treatment with 5 U/day restored the isoenzyme distribution to normal. These results indicate that gross cardiac contractile function can be normalized with insulin dosages that are not sufficient to correct hyperglycemia, polydipsia, or body and heart weight.(ABSTRACT TRUNCATED AT 250 WORDS)