Type 2 Diabetes Complicated With Heart Failure: Research on Therapeutic Mechanism and Potential Drug Development Based on Insulin Signaling Pathway

Abstract

Type 2 diabetes mellitus (T2DM) and heart failure (HF) are diseases characterized by high morbidity and mortality. They often occur simultaneously and increase the risk of each other. T2DM complicated with HF, as one of the most dangerous disease combinations in modern medicine, is more common in middle-aged and elderly people, making the treatment more difficult. At present, the combination of blood glucose control and anti-heart failure is a common therapy for patients with T2DM complicated with HF, but their effect is not ideal, and many hypoglycemic drugs have the risk of heart failure. Abnormal insulin signaling pathway, as a common pathogenic mechanism in T2DM and HF, could lead to pathological features such as insulin resistance (IR), myocardial energy metabolism disorders, and vascular endothelial disorders. The therapy based on the insulin signaling pathway may become a specific therapeutic target for T2DM patients with HF. Here, we reviewed the mechanisms and potential drugs of insulin signaling pathway in the treatment of T2DM complicated with HF, with a view to opening up a new perspective for the treatment of T2DM patients with HF and the research and development of new drugs.

Bioinformatics prediction and experimental verification of a novel microRNA for myocardial fibrosis after myocardial infarction in rats

“…The insulin signaling pathway is a common signaling pathway to regulate myocardial energy metabolism. The binding of insulin to the corresponding receptor can phosphorylate insulin substrate, thus activating PI3K/Akt signaling pathway ( Ye et al, 2022 ). The phosphorylation of Akt leads to the phosphorylation of many downstream targets, such as GSK-3β, mediating the cell growth and proliferation and glucose metabolism regulation ( Plotnikov et al, 2011 ).…”

“…There are severe systemic and myocardial glucose metabolism disorders in T2DM patients complicated with heart failure, resulting in significant abnormalities of myocardial energy metabolism and dysfunction of myocardial contraction. The insulin signaling pathway can improve abnormal energy metabolism in the whole body and myocardium, in which the core is the activation of Akt ( Ye et al, 2022 ). However, over-expression of Akt can cause pathological myocardial hypertrophy ( Dorn & Force, 2005 ).…”

N6-methyladenosine (m 6 A) IGF2BP1 regulates high glucose-induced vascular endothelial cells apoptosis via targeting HMGB1

“…N 6 -methyladenosine (m 6 A), the most common RNA chemical modi cation on posttranscription, could participate in numerous pathophysiological processes (Dhawan, et al, 2022, Ye, et al, 2022. In the vasculopathy, more and more literatures have indicated the essential roles of m 6 A.…”

Therapeutic Potential of Metformin in Diabetes Mellitus-Related Cardiovascular Complications

“…The molecular mechanism initiating DCM is unclear, but the major clinical and biochemical dysfunctions in DCM development have been identified, such as hyperglycemia, systemic insulin resistance, and impaired cardiac insulin signaling [60][61][62]. Emerging evidence highlights the significance of abnormal mitochondrial function and energy metabolism in causing pathological remodeling of the cardiac structure [63,64]. Metformin has been shown to be cardioprotective in ongoing clinical and basic research and it has been recommended as first-line therapy in diabetic patients with heart failure (HF) based on clinical practice guidelines [65].…”