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The impact of p38 MAPK, 5-HT/DA/E signaling pathways in the development and progression of cardiovascular diseases and heart failure in type 1 diabetes

Molecular and Cellular Research Unit, Kongunadu Arts and Science College, Bharathiar University, India

Serotonin or 5-HT, DA and E, all monoamine neurotransmitters, work also as hormones, plays crucial role in the brain and body. This 5-HT, DA and E increased significantly, and regulated by activated p38 MAPK in type I diabetes mellitus (T1DM), and that has been shown to involve in metabolic disorders as well as cardiovascular diseases, leading to heart failure. Even though these molecules are being considered for clinical trials in the treatments of various cardiovascular diseases, the synergistic-pathophysiological mechanisms of these p38 MAPK and neurotransmitters on target molecules, cells and tissues in heart failure are not completely understood in T1DM. However, T1DM results in metabolic dysregulation, impairment/loss of insulin secretion, hyperglycemia and acidosis. These changes are widely reported to be involved in abnormal functions of receptors, which provide binding site for signaling molecules. We are constantly focusing on the mechanisms of alloxan-induced-diabetes, glucose-induced-hyperglycemia and ammonium chloride-induced-acidosis (non-diabetic hyperglycemia (NDH) and non-diabetic acidosis (NDA), respectively) on the levels and functions of neurotransmitters and p38 MAPK. Here, in this review, we are proposing the mechanisms of insulin and/or some of the pharmacological agents on the level and functions of p38 MAPK and neurotransmitters in various areas of rat brain under diabetic or its associated conditions, which leads to cardiovascular dysfunctions. Targeting these molecules/pathways may be useful in the treatment of cardiovascular diseases and diabetes mediated heart failure.
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