Effect of transient elevation of glucose on contractile properties in non-diabetic rat cardiac muscle

Masahito Miura, Taiki Hasegawa, Ayana Matsumoto, Masami Nishiyama, Yuka Someya, Wakako Satoh, Kazunori Kumasaka, Chiyohiko Shindo, Haruka Sato

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

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 Ca2+ ([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 Ca2+/calmodulin-dependent 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 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.

Original languageEnglish
Pages (from-to)568-576
Number of pages9
JournalHeart and Vessels
Volume36
Issue number4
DOIs
Publication statusPublished - 2021 Apr
Externally publishedYes

Keywords

  • Calcium
  • CaMKII
  • Cardiac muscle contraction
  • Glucose

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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