Effect of transient elevation of glucose on contractile properties in non-diabetic rat cardiac muscle
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ORIGINAL ARTICLE
Effect of transient elevation of glucose on contractile properties in non‑diabetic rat cardiac muscle Masahito Miura1 · Taiki Hasegawa1 · Ayana Matsumoto1 · Masami Nishiyama1 · Yuka Someya1 · Wakako Satoh1 · Kazunori Kumasaka1 · Chiyohiko Shindoh1 · Haruka Sato1 Received: 13 May 2020 / Accepted: 6 November 2020 © Springer Japan KK, part of Springer Nature 2020
Abstract 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 C a2+ ([Ca2+]i), and sarcomere length were measured in trabeculae from rat hearts. To assess contractile properties, maximum velocity of contraction (Max dF/dt) and minimum velocity of relaxation (Min dF/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, Max dF/dt, and Min dF/dt were reduced without changes in [ Ca2+]i transients at 2.5 Hz stimulation and 2.0 mM [ Ca2+]o, while developed force and [ Ca2+]i transients showed no changes at 0.5 Hz stimulation and 0.7 mM [ Ca2+]o. In the presence of 1 μM KN-93, a C a2+/calmodulindependent protein kinaseII (CaMKII) inhibitor, or 50 μM diazo-5-oxonorleucine, a l-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 C a2+-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. Keywords Glucose · Cardiac muscle contraction · Calcium · CaMKII
Introduction Admission blood glucose level is associated with increased in-hospital [1–3] and 30-day mortality [4, 5] in non-diabetic patients with acute myocardial infarction or unstable angina. Also in non-diabetic patients with acute heart failure, admission glucose level is associated with higher in-hospital, 30-day, 60-day, and long-term (1.8 years) mortality [6–9], while in elderly patients with heart failure, it is not associated with 30-day and 1-year mortality [10]. In the patients with severe disease, transient increase in blood glucose occurs due to stress and has been called “stress hyperglycemia” [11]. It has not yet been determined in the past * Masahito Miura [email protected] 1
Department of Clinical Physiology, Health Science, Tohoku University Graduate School of Medicine, 2‑1 Seiryo‑machi, Aoba‑ku, Sendai, Miyagi 980‑8574, Japan
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