Acute effects of euglycemic-hyperinsulinemia on myocardial contractility in male mice.
Acute effects of euglycemic-hyperinsulinemia on myocardial contractility in male mice.
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DOI：
10.14814/phy2.15388
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发表时间：
2022-09
影响因子：
2.5
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中科院分区：
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2型糖尿病和肥胖与心血管疾病的风险增加有关，包括心力衰竭。这些代谢异常状态的标志是高胰岛素血症和心脏储备下降。然而，高胰岛素血症对心肌功能的直接影响还不完全清楚。在这项研究中，我们使用小鼠的侵入性血流动力学，研究了短期血糖正常的高胰岛素血症对基础心肌功能的影响以及心肌对β肾上腺素能刺激的后续反应。我们发现，通过左心室（LV）侵入性血流动力学测量的心脏功能不受静脉注射胰岛素诱导的高胰岛素血症急性暴露的影响，同时伴有异丙肾上腺素给药后β肾上腺素能刺激诱导的正性肌力刺激。当动物通过正葡萄糖-高胰岛素钳夹暴露于120分钟的高胰岛素血症时，LV发展压力显著降低，可能继发于胰岛素的全身血管舒张作用。尽管基线降低，但在接受正常血糖高胰岛素钳夹的动物中，对β-肾上腺素能刺激的收缩反应保持完整。受磷蛋白磷酸化的β-肾上腺素能激活不受高胰岛素血症的损害。这些结果表明，短期高胰岛素血症不会损害体内对β肾上腺素能刺激的心脏变力反应。急性血糖正常的高胰岛素血症不会损害基线心脏功能或其对β-肾上腺素能刺激诱导的变力性的反应。
Type 2 diabetes and obesity are associated with increased risk of cardiovascular disease, including heart failure. A hallmark of these dysmetabolic states is hyperinsulinemia and decreased cardiac reserve. However, the direct effects of hyperinsulinemia on myocardial function are incompletely understood. In this study, using invasive hemodynamics in mice, we studied the effects of short‐term euglycemic hyperinsulinemia on basal myocardial function and subsequent responses of the myocardium to β‐adrenergic stimulation. We found that cardiac function as measured by left ventricular (LV) invasive hemodynamics is not influenced by acute exposure to hyperinsulinemia, induced by an intravenous insulin injection with concurrent inotropic stimulation induced by β‐adrenergic stimulation secondary to isoproterenol administration. When animals were exposed to 120‐min of hyperinsulinemia by euglycemic‐hyperinsulinemic clamps, there was a significant decrease in LV developed pressure, perhaps secondary to the systemic vasodilatory effects of insulin. Despite the baseline reduction, the contractile response to β‐adrenergic stimulation remained intact in animals subject to euglycemic hyperinsulinemic clamps. β‐adrenergic activation of phospholamban phosphorylation was not impaired by hyperinsulinemia. These results suggest that short‐term hyperinsulinemia does not impair cardiac inotropic response to β‐adrenergic stimulation in vivo. Acute euglycemic hyperinsulinemia does not impair baseline cardiac function or its response to beta‐adrenergic stimulation induced inotropy.