Abstract 18770: Dysregulation of miR-301b Contributes to Diabetic Cardiomyopathy via Upregulation of AMP Deaminase in the Vicinity of the Sarcoplasmic Reticulum

Background: Diabetic cardiomyopathy is a major risk factor of HFpEF, which often decompensates under increased afterload. We recently found that excessive degradation of ATP by upregulated AMP deaminase (AMPD) contributes to marked enhancement of diastolic dysfunction at the time of increased afterload in a rat model of type 2 diabetes (T2D), OLETF. Upregulation of AMPD by T2DM appears to be shared with other animal models of T2D according to the Gene Expression Omnibus, a public genomics data repository. Here we examined the mechanism by which the activity of AMPD is upregulated by T2D. Methods and Results: AMPD activity in the ventricular tissue of OLETF was higher by 60% than that in LETO, non-diabetic control rats. Factors known to regulate AMPD activity, including PKC-mediated phosphorylation, were similar in OLETF and LETO. Western blot analysis revealed that protein level of the 90-kDa full-length form AMPD3 (a dominant isoform in rat hearts), but not that of the 78-kDa N-terminus truncated form AM...