The crucial role and mechanism of insulin resistance in metabolic disease

Abstract

Insulin resistance (IR) plays a crucial role in the development and progression of metabolism-related diseases such as diabetes, hypertension, tumors, and nonalcoholic fatty liver disease, and provides the basis for a common understanding of these chronic diseases. In this study, we provide a systematic review of the causes, mechanisms, and treatments of IR. The pathogenesis of IR depends on genetics, obesity, age, disease, and drug effects. Mechanistically, any factor leading to abnormalities in the insulin signaling pathway leads to the development of IR in the host, including insulin receptor abnormalities, disturbances in the internal environment (regarding inflammation, hypoxia, lipotoxicity, and immunity), metabolic function of the liver and organelles, and other abnormalities. The available therapeutic strategies for IR are mainly exercise and dietary habit improvement, and chemotherapy based on biguanides and glucagon-like peptide-1, and traditional Chinese medicine treatments (e.g., herbs and acupuncture) can also be helpful. Based on the current understanding of IR mechanisms, there are still some vacancies to follow up and consider, and there is also a need to define more precise biomarkers for different chronic diseases and lifestyle interventions, and to explore natural or synthetic drugs targeting IR treatment. This could enable the treatment of patients with multiple combined metabolic diseases, with the aim of treating the disease holistically to reduce healthcare expenditures and to improve the quality of life of patients to some extent.

Molecular Mechanisms of the Vicious Cycle between Insulin Resistance and the Inflammatory Response in Obesity

“…Given that there is a linking mechanism between obesity, inflammation, and IR, the predominance of the type 1 inflammatory response in AT may be involved in the etiopathogenesis of altered insulin signaling. In contrast to AT type 1 inflammation in obesity, type 2 inflammatory conditions are a part of AT immune homeostasis regulation in lean healthy individuals [111,159]. It has been suggested that the initiation of generalized low-grade inflammation in obesity may be triggered by the production of chemokines by adipose cells, the release of damage-associated molecular patterns (DAMPs) from necrotic AT, augmented rates of lipolysis with a subsequent increase in the flux of nonesterified fatty acids, and hypoxia with activation of hypoxia-induced factor (HIF)-1, which controls the expression of proinflammatory proteins [160].…”

“…Apart from the dominant result of IR, which is T2DM, the metabolic consequences of IR include a broad spectrum of diseases and pathologic conditions, such as hypertension, dyslipidemia, visceral adiposity, nonalcoholic fatty liver disease (NAFLD), ovarian dysfunction and hyperandrogenism in women, acromegaloid features, hyperuricemia, elevated inflammatory markers, endothelial dysfunction, a prothrombic state, cancer, and neurodegenerative disorders, including AD [107][108][109][110]. Consequently, IR is a permanent component of metabolic syndrome, a cluster of conditions that occur together, increasing the risk of heart disease, stroke and T2DM [111]. In addition, an early and common manifestation of severe IR is skin changes known as acanthosis nigricans that usually develop in skin folds, such as the back of the neck, axilla and groin, and involve darkening and thickening of the skin (velvety overgrowth of the epidermis) [108].…”

MHO or MUO? White adipose tissue remodeling

“…It serves as an inevitable precursor to the development of type 2 diabetes mellitus (T2DM) and may also be a trigger for cardiovascular diseases (CVDs). Given that IR is a pivotal unifying factor in MetS, 8 the refined pathophysiological definition of MHO may primarily hinge on insulin sensitivity 9 . Despite the contentious clinical significance of MHO as a “diagnosis,” it offers a distinctive human model system for investigating the underlying mechanisms promoting weight gain and metabolic health.…”

The correlation between visceral fat area to skeletal muscle mass ratio and multi-organ insulin resistance in Chinese population with obesity: a cross-sectional study

“…IR is one of the main pathological mechanisms of obesity and cardiometabolic diseases, which plays an important role in the development of cardiometabolic diseases [9] . Research clearly showed that IR is closely related to visceral adiposity and patients with IR are more likely to have microvascular complications and cardiometabolic diseases [3,9] .…”

“…IR is one of the main pathological mechanisms of obesity and cardiometabolic diseases, which plays an important role in the development of cardiometabolic diseases [9] . Research clearly showed that IR is closely related to visceral adiposity and patients with IR are more likely to have microvascular complications and cardiometabolic diseases [3,9] . Therefore, the aim of present study was to investigate the relationship between VSR and multi-organ IR, which could lay down the pathophysiological mechanisms for further revealing the relationship between VSR and cardiometabolic diseases.…”