Insulin resistance and hyperinsulinaemia in diabetic cardiomyopathy

By Guanghong Jia, V. DeMarco, J. Sowers. Nature Reviews Endocrinology, 2015

821 citations recorded by the source corpus.

Insulin resistance, type 2 diabetes mellitus and associated hyperinsulinaemia can promote the development of a specific form of cardiomyopathy that is independent of coronary artery disease and hypertension. Termed diabetic cardiomyopathy, this form of cardiomyopathy is a major cause of morbidity and mortality in developed nations, and the prevalence of this condition is rising in parallel with increases in the incidence of obesity and type 2 diabetes mellitus. Of note, female patients seem to be particularly susceptible to the development of this complication of metabolic disease. The diabetic cardiomyopathy observed in insulin- resistant or hyperinsulinaemic states is characterized by impaired myocardial insulin signalling, mitochondrial dysfunction, endoplasmic reticulum stress, impaired calcium homeostasis, abnormal coronary microcirculation, activation of the sympathetic nervous system, activation of the renin–angiotensin–aldosterone system and maladaptive immune responses. These pathophysiological changes result in oxidative stress, fibrosis, hypertrophy, cardiac diastolic dysfunction and eventually systolic heart failure. This Review highlights a surge in diabetic cardiomyopathy research, summarizes current understanding of the molecular mechanisms underpinning this condition and explores potential preventive and therapeutic strategies.

Subfields: Cardiology and Cardiovascular Medicine, Endocrinology, Diabetes and Metabolism, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/ef6333c71d0f9d848037e4d09215eaf8dc843297

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cardiology and Cardiovascular Medicine

1. M. Hill
2. Guanghong Jia
3. J. Sowers

In Endocrinology, Diabetes and Metabolism

1. M. Hill
2. Guanghong Jia
3. J. Sowers
4. Barry J. Goldstein
5. Rosario Scalia

In Molecular Biology

1. M. Hill
2. Guanghong Jia
3. J. Sowers
4. Jian Li

Citations in the corpus

• Diabetic vascular diseases: molecular mechanisms and therapeutic strategies (2023, background): “Lipid accumulation and fatty acids-induced lipotoxicity can affect myocardial FAO processes, promote endoplasmic reticulum (ER) stress, autophagy, and apoptosis, and cause ventricular remodeling.(20,30) The most important metabolites of diabetic glycotoxin are advanced glycation end-products (AGEs) ”
• Diabetic cardiomyopathy: a hyperglycaemia- and insulin-resistance-induced heart disease (2017, background): “In this context, the clinical course of cardiac dysfunction in diabetes progresses from subclinical cardiac abnormalities, such as left ventricular fibrosis and diastolic dysfunction, to severe diastolic heart failure with normal ejection fraction and eventually to systolic dysfunction accompanied b”
• Obesity and type 2 diabetes mellitus: connections in epidemiology, pathogenesis, and treatments (2023, background): “Given the suppression of autophagy in overnutrition, the downregulated secretion of glucagon under nutrient excess leads to hyperinsulinemia that blunts autophagy, compromising insulin signaling in return and boosting the development of T2DM (100).”
• Triglyceride-glucose index as a marker in cardiovascular diseases: landscape and limitations (2022, background): “In patients with cardiac ischaemia, IR is inversely associated with median colony forming unit endothelial cells, contributing to a reduced density of collaterals in response to cardiac ischaemia [68].”
• Insulin resistance, cardiovascular stiffening and cardiovascular disease. (2021, neutral): “Of further translational relevance, obese and insulin resistant women increasingly constitute a growing population of individuals with HFpEF [25,27] as well as overall CVD. [6,54].”
• Diabetic cardiomyopathy: an update of mechanisms contributing to this clinical entity (2018, methodology): “chamber, shortened ejection period, and the latter by an increased resistance to filling with increased filling pressures.(13)”
• Association between insulin resistance and the development of cardiovascular disease (2018, background): “This binding activates receptor autophosphorylation, which triggers a downstream signaling cascade through the phosphorylation of tyrosine residues of the insulin receptor substrates, IRS (IRS-1 or IRS-2), followed by phosphorylation of phosphatidylinositol 3-kinase (PI3K), phosphoinositide dependen”