Gender related differential effects of Omega-3E treatment on diabetes-induced left ventricular dysfunction

Abstract

The present study was designed to determine whether there are beneficial effects of intake of Omega-3E (containing 70% pure omega-3 and 2% natural vitamin E) in cardiac dysfunction of diabetic rats. We also examined whether there are gender-related differences in the responses to the intake of Omega-3E on the heart dysfunction. Experiments were performed by using Langendorff-perfused hearts from normal, diabetic (with 50 mg/kg streptozotocin), and Omega-3E (50 mg/kg body weight/day) treated diabetic 3-month-old Wistar rats. Omega-3E treatment of the diabetics caused small, but significant decrease (13% and 14% female versus male) in the blood glucose level. Omega-3E treatment of the diabetic female rats did not prevent diabetes-induced decrease in left ventricular developed pressure (LVDP) and increase in left ventricular end-diastolic pressure (LVEDP) with respect to the control female rats. On the other hand, the treatment of diabetic male rats caused significant recovery in depressed LVDP. Furthermore, such treatment of diabetic female and male rats caused significant recovery in depressed rates of changes of developed pressure. This effect was more significant in males. Besides, Omega-3E caused significant further lengthening in the diabetes-induced increased time to the peak of the developed pressure in females, while it normalized the lengthening in the relaxation of the developed pressure in diabetic males. In addition, Omega-3E treatment caused significant restorations in the diabetes-induced altered activities of antioxidant enzymes without any significant gender discrepancy. Present data show that there are gender related differences in diabetic heart dysfunction and the response to antioxidant treatment.

Impact of sex on the heart's metabolic and functional responses to diabetic therapies

“…This was not mediated by a hemodynamic change. This result agrees with findings in a type 1 diabetes rat model in which males exhibited greater diastolic function improvement than females (22). The mechanism of this sexually dimorphic response is not clear.…”

“…Conversely, lowering plasma FA levels in animals with T2DM prevents heart lipid accumulation and cardiac dysfunction (25). Animals with T2DM treated with omega-3E fatty acids, which typically lower plasma triglyceride levels, also improved cardiac dysfunction, but only in the males (22). A study in T2DM men showed that lowering plasma FA levels (via weight loss) was associated with lower myocardial fat accumulation and improved diastolic function (23).…”

Intracellular Zn2+ Increase in Cardiomyocytes Induces both Electrical and Mechanical Dysfunction in Heart via Endogenous Generation of Reactive Nitrogen Species

“…To mimic type 1 diabetes mellitus, we injected male Wistar rats (initial body weight, 200-230 g) with 50 mg/kg streptozotocin (STZ), intraperitoneally, as described previously [24]. One week after injection of STZ, blood glucose level was measured with glucostix reagent strips by a glucometer and the rats with 3-fold higher levels of blood glucose than pre-injection levels were used as diabetic animals.…”

Sex and Gender Differences in Endocrinology

“…47 Omega-3E supplementation appears much more effective in the prevention of DM-related left ventricular damage in male animals than in females. 48 In transgenic diabetic male mice, the contractile function of cardiomyocytes was found to be reduced due to differences in Akt activation between the sexes. 49 Phospholamban protein levels and thus cardiac contraction differed between males and females, 50 whereas sex differences in actomyosin crossbridge kinetics of myofi laments were abolished by DM in diabetic rat hearts.…”