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. 2021 Apr 30;129(1):98–113. doi: 10.1161/CIRCRESAHA.120.318402

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© 2021 The Authors.

Circulation Research is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDerivs License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited, the use is noncommercial, and no modifications or adaptations are made.

This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.

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Figure 5. — Diabetes-induced cardiac remodeling and arrhythmias are dependent on CaMKIIδ (Ca²⁺/calmodulin-dependent protein kinase II) activation. A, Study protocol of streptozotocin (STZ)-induced diabetes and assessment of cardiac function. B, Blood glucose levels were highly elevated, whereas cardiac ejection fraction was preserved in STZ. Wilcoxon matched-pairs signed-rank test. C, Morphological parameters in either vehicle-treated or STZ-treated CaMKIIδ-wild type (WT), S280A, and mutated Met281Val and Met282Val (MMVV) mice. One-way ANOVA, followed by Dunnett multiple comparisons test. D, Preserved systolic heart function in STZ. E, Diastolic heart function (enlarged left atria, reduced E/A, increased E/e′) in 4-week diabetes. One-way ANOVA, followed by Dunnett multiple comparisons test. F, Incidence of premature ventricular complexes (PVCs) following isoproterenol+caffeine stress test was increased in diabetic WT animals, whereas CaMKIIδ-cardiac-specific knockout (cKO) was protective. Mann-Whitney test. G, Increased RyR (ryanodine receptor) S2814 phosphorylation and PLB (phospholamban) O-GlcNAcylation in STZ. Two technical replicates (blots) were performed for each protein sample. Mann-Whitney test. The number of biological replicates (n) is shown. HW/BW indicates heart weight to body weight ratio; IVS, interventricular septum; LA, left atrial; and LV, left ventricular.