Figure 1. Overview of dysregulated major signalling pathways dysregulated in diabetic cardiomyopathy.

Diabetes-induced molecular impairments lead to cardiac remodelling, inflammation, oxidative stress and impaired calcium handling, contributing to cardiac dysfunction that initially develops as diastolic dysfunction. Over time, impairment of endothelial and smooth muscle cells in the vasculature can lead to reduced coronary microvascular blood flow, as a result of this microvascular dysfunction. The dysfunction in the vasculature and the myocardium can eventually lead to LV systolic dysfunction; Akt, protein kinase B; CTGF, connective tissue growth factor; eNOS, endothelial nitric oxide synthase; HBP, hexosamine biosynthesis pathway; LV, left ventricular; NFκB, nuclear factor-κB; Nox, NADPH oxidase; PI3K, phosphoinositide-3 kinase; PKC, protein kinase-C; PLN, phospholamban; ROS, reactive oxygen species; SERCA2a, sarcoplasmic/endoplasmic reticulum ATPase- Ca²⁺; TGF-β, transforming growth factor-β; TNFα, tumour necrosis factor-α (see text for references).