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Effects of myo-inositol and, or triiodothyronine (T₃) treatment on cardiac dysfunction and elevated myocardial lipid levels in STZ-diabetic rats

University of British Columbia

A number of experimental studies have implied a link between diabetes-induced lipid accumulation in the myocardium and the development of cardiomyopathy. Since diabetics excrete large amounts of myo-inositol which is a lipotropic agent, this study was undertaken to investigate the effects of myo-inositol on the elevated myocardial lipid levels and the depressed cardiac performance of diabetic rats. Diabetes was induced in female Wistar rats (190-215 g) with streptozotocin (STZ) (55 mg/kg, i.v.). Three days after diabetes induction, myo-inositol was administered in the drinking water (2.5 g/kg/day) for a 8 week period. Untreated diabetics exhibited a loss of body weight, hyperglycemia, hypoinsulinemia and hypothyroidism. These effects were not altered after myo-inositol treatment. STZ-diabetes also produced a significant elevation of plasma and myocardial triacylglycerol, cholesterol and phospholipid. Myo-inositol treatment decreased these lipid levels. In addition, hearts from diabetic animals had a decreased ability to develop left ventricular developed pressure (LVDP) and both the rate of pressure rise (+dP/dt) and the rate of pressure decline (-dP/dt) were also reduced. Hearts from myo-inositol-treated diabetic animals showed a partial but definite improvement of cardiac function. As diabetes-induced hypothyroidism was not altered after myo-inositol supplementation, a combination treatment of both myo-inositol (2.5 g/kg/day, p.o. daily) and T₃ (30 ug/kg/day, s.c. daily) was then undertaken to determine whether heart function of diabetic rats could be further improved. STZ-diabetic rats were characterized by a loss of body weight, hyperglycemia and hypoinsulinemia; none of which were altered by either T₃ or myo-inositol plusT₃ treatment. T₃ treatment normalized the thyroid state of diabetic animals as shown by Tahiliani and McNeill (1984). However, plasma and myocardial triacylglycerol, cholesterol and phospholipid levels of diabetic rats either remained elevated or were further increased with T₃ or myo-inositol plus T₃ treatment. In addition, T₃ treatment alone did not prevent cardiac dysfunction in diabetic rats. There was, however, some improvement in heart function in the groups treated with both myo-inositol and T₃, but the improvement was not as pronounced as with myo-inositol treatment alone.

Text

2010-07-20

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http://hdl.handle.net/2429/26675

Pharmaceutical Sciences

University of British Columbia

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