Effect of transient elevation of glucose on contractile properties in non-diabetic rat cardiac muscle
Effect of transient elevation of glucose on contractile properties in non-diabetic rat cardiac muscle
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DOI：
10.1007/s00380-020-01726-6
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发表时间：
2020-11
影响因子：
1.5
通讯作者：
M. Miura;T. Hasegawa;A. Matsumoto;M. Nishiyama;Y. Someya;W. Satoh;K. Kumasaka;C. Shindoh;Haruka Sato
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文献类型：
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作者：
M. Miura;T. Hasegawa;A. Matsumoto;M. Nishiyama;Y. Someya;W. Satoh;K. Kumasaka;C. Shindoh;Haruka Sato
非糖尿病重症患者，如急性心肌梗死或急性心力衰竭，入院时血糖水平与其短期和长期死亡率相关。我们研究了葡萄糖的短暂升高是否会影响非糖尿病心脏的收缩特性。在大鼠心脏小梁中测量了力、细胞内Ca2+([Ca2+]i)和肌节长度。为了评估收缩性能，计算最大收缩速度（MaxdF/dt）和最小松弛速度（MindF/dt）。测定磷酸化肌钙蛋白I （P-TnI）与肌钙蛋白I （TnI）的比值。葡萄糖从150毫克/分升到400毫克/分升1小时后，2.5 Hz和2.0 mM [Ca2+] 0刺激下，发育力、MaxdF/dt和MindF/dt降低，但[Ca2+]瞬变没有变化，而0.5 Hz和0.7 mM [Ca2+] 0刺激下，发育力和[Ca2+]瞬变没有变化。在1 μM KN-93 （Ca2+/钙调素依赖性蛋白激酶ii （CaMKII）抑制剂）或50 μM重氮-5-oxonorleucine， al-谷氨酰胺-d-果糖-6-磷酸氨基转移酶抑制剂)存在下，葡萄糖升高后收缩特性的降低被抑制。此外，在2.0 mM [Ca2+]o下，葡萄糖升高至400 mg/dL 1 h后，P-TnI与TnI的比值增加。这些结果表明，在高Ca2+负荷的非糖尿病心脏中，葡萄糖短暂升高1小时可能通过o - glcn酰化激活CaMKII来降低收缩特性。因此，在病情严重的患者中，短暂的血糖升高，如由于应激，可能使心功能恶化，从而影响其无已知糖尿病的死亡率。
In non-diabetic patients with severe disease, such as acute myocardial infarction or acute heart failure, admission blood glucose level is associated with their short-term and long-term mortality. We examined whether transient elevation of glucose affects contractile properties in non-diabetic hearts. Force, intracellular Ca2+([Ca2+]i), and sarcomere length were measured in trabeculae from rat hearts. To assess contractile properties, maximum velocity of contraction (MaxdF/dt) and minimum velocity of relaxation (MindF/dt) were calculated. The ratio of phosphorylated troponin I (P-TnI) to troponin I (TnI) was measured. One hour after elevation of glucose from 150 to 400 mg/dL, developed force, MaxdF/dt, and MindF/dtwere reduced without changes in [Ca2+]itransients at 2.5 Hz stimulation and 2.0 mM [Ca2+]o, while developed force and [Ca2+]itransients showed no changes at 0.5 Hz stimulation and 0.7 mM [Ca2+]o. In the presence of 1 μM KN-93, a Ca2+/calmodulin-dependent protein kinaseII (CaMKII) inhibitor, or 50 μM diazo-5-oxonorleucine, al-glutamine-d-fructose-6-phosphate amidotransferase inhibitor, the reduction of contractile properties after elevation of glucose was suppressed. Furthermore, 1 h after elevation of glucose to 400 mg/dL at 2.0 mM [Ca2+]o, the ratio of P-TnI to TnI was increased. These results suggest that in non-diabetic hearts under higher Ca2+-load, transient elevation of glucose for 1 h reduces contractile properties probably by activating CaMKII through O-GlcNAcylation. Thus, in the patients with severe disease, transient elevation of blood glucose, such as due to stress, may worsen cardiac function and thereby affect their mortality without known diabetes.