Diabetic Cardiomyopathy
(DAG) and ceramides impair insulin metabolic signaling and prompt diabetic cardiomyopathy. In this regard, the increased DAG in cardiomyocytes impairs glucose metabolism through activation of protein kinase C (PKC) isoforms [24]. Ceramides are a family of bioactive waxy lipid molecules composed of sphingosine and a fatty acid [24]. Ceramide directly activates the atypical PKCs to phosphorylate and inhibit the insulin metabolic Akt/PKB signaling and thus inhibit GLUT4 translocation and insulin-stimulated glucose uptake [24]. Therefore, lipid accumulation and its lipid metabolites contribute to cardiac insulin resistance and dysfunction.
Mitochondrial dysfunction and oxidative stress
The increased mitochondrial fatty acid uptake and β-oxidation …show more content…
One study has found that hyperglycemia induced activation of RAAS that increased mean arterial pressure, renal vascular resistance and vasomotor tone [29]. Losartan, an antagonist of angiotensin II receptor 1, decreased greater blood pressure in hyperglycemic than in euglycemic conditions [30]. Large randomized controlled trials including RALES, EPHESUS, and EMPHASIS have demonstrated that inhibition of aldosterone role through blocking its mineralocorticoid receptor decrease morbidity and mortality and in both mild and moderately severe heart failure [31]. Immune cells including macrophages, dendritic cells and activated T lymphocytes have been found to involved in diabetic cardiomyopathy [4]. The proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and monocyte chemotactic protein 1 (MCP-1), released from cardiomyocytes and other activated immune cells, contribute to cardiac oxidative stress and coronary artery dysfunction, ultimately leading to cardiac remodeling, fibrosis, and diastolic dysfunction [4]. Furthermore, macrophage M1 polarization in favoring inflammation response is increased whereas macrophage M2 anti-inflammatory response is inhibited in diabetic heart tissues [4]. Thus, systemic and local maladaptive inflammation responses play a key roles in the cardiac remodeling and fibrosis that can progress to clinical heart
Mitochondrial dysfunction and oxidative stress
The increased mitochondrial fatty acid uptake and β-oxidation …show more content…
One study has found that hyperglycemia induced activation of RAAS that increased mean arterial pressure, renal vascular resistance and vasomotor tone [29]. Losartan, an antagonist of angiotensin II receptor 1, decreased greater blood pressure in hyperglycemic than in euglycemic conditions [30]. Large randomized controlled trials including RALES, EPHESUS, and EMPHASIS have demonstrated that inhibition of aldosterone role through blocking its mineralocorticoid receptor decrease morbidity and mortality and in both mild and moderately severe heart failure [31]. Immune cells including macrophages, dendritic cells and activated T lymphocytes have been found to involved in diabetic cardiomyopathy [4]. The proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and monocyte chemotactic protein 1 (MCP-1), released from cardiomyocytes and other activated immune cells, contribute to cardiac oxidative stress and coronary artery dysfunction, ultimately leading to cardiac remodeling, fibrosis, and diastolic dysfunction [4]. Furthermore, macrophage M1 polarization in favoring inflammation response is increased whereas macrophage M2 anti-inflammatory response is inhibited in diabetic heart tissues [4]. Thus, systemic and local maladaptive inflammation responses play a key roles in the cardiac remodeling and fibrosis that can progress to clinical heart