Glucose-induced cell signaling in the pathogenesis of diabetic cardiomyopathy

Abstract

Chronic diabetic complications affect multiple organ systems and lead to significant morbidity and mortality in the diabetic population. Diabetic cardiomyopathy is a major etiologic factor causing heart failure. Dysfunction of both vascular endothelial cells and cardiomyocytes contributes in the pathogenesis of diabetic cardiomyopathy. Hyperglycemia has been identified as the key determinant in the development of several chronic diabetic complications. Hyperglycemia leads to oxidative stress and several other abnormalities causing changes in cellular signaling. These diabetes-mediated biochemical anomalies show cross-interaction and complex interplay. Such changes also cause alteration of transcriptional and post-transcriptional machinery causing altered production of vasoactive and cardioactive factors. In this review, we will highlight some of the important signaling changes leading to diabetic cardiomyopathy and discuss possible potential therapeutic remedies.

GW0742 activates peroxisome proliferator‐activated receptor δ to reduce free radicals and alleviate cardiac hypertrophy induced by hyperglycemia in cultured H9c2 cells

“…The development of diabetic cardiomyopathy is associated with oxidative stress from elevated ROS production and/or decreased antioxidant defense . Abnormal metabolites induced by diabetes, such as hyperglycemia in the heart, cause ROS . Therefore, a HG‐induced cardiac hypertrophy model has been established in H9c2 cells .…”

“…Cardiac hypertrophy is associated with increased free radicals . Abnormal metabolites induced by diabetes, similar to hyperglycemia in the heart, cause the production of free radicals . Therefore, HG‐induced cardiac hypertrophy in H9c2 cells is widely associated with free radicals.…”

Assessment of Inflammatory and Cardiovascular Markers in Type 2 Diabetes without Clinical Evidence of Cardiac Events

“…*p=0.003, **p=0.001 compared with negative C-reactive protein vasoactive and cardioactive factors. Therefore, dysfunction of both vascular endothelial cells and cardiomyocytes play a role in the pathogenesis of diabetic cardiomyopathy (16). Accordingly, the endothelial dysfunction occurring in T2D is associated with changes in vas-regulation (demonstrated by low serum NO), inflammatory activation (demonstrated by positive C-reactive protein test), and altered cardiac cell function (demonstrated by high serum NT-proBNP level) (17).…”

The GLP-1 Analogue Liraglutide Protects Cardiomyocytes from High Glucose-induced Apoptosis by Activating the Epac-1/Akt Pathway

“…High glucoseinduced reactive oxygen species (ROS) generation can lead to diabetic cardiomyopathy [23]. Hyperglycemia and oxidative stress are the major mechanisms that cause cardio myocyte apoptosis in diabetic cardiomyopathy [24]. Glucagon like peptide1 (GLP1) is an incretin that is rapidly released after meal intakes.…”