Mechanistic and Physiological Implications of Insulin Resistance in Metabolic Diseases

Maintaining physiological insulin homeostasis is the result of a balance between insulin secretion and clearance. Insulin resistance is conceived as a defect in insulin-mediated control of glucose metabolism in tissues such as muscle, liver, and adipose tissue and is one of the earliest manifestations of a constellation of human diseases, including type 2 diabetes and cardiovascular disease. Insulin resistance is caused by a complex combination of genetic and environmental factors. Despite many advances in the last decades, the mechanisms underlying insulin resistance are not yet fully understood. Recent evidence suggests a key role of different tissues in the development of insulin resistance, potentially by releasing lipids and other circulating factors. These extracellular factors may cause insulin resistance by inhibiting one or more of the key components of the signaling cascade downstream of insulin. This Special Issue focuses on presenting a comprehensive view of the regulation of insulin homeostasis with an overarching goal to highlight the current knowledge on the mechanisms as well as the physiological impact of altered insulin secretion, clearance, and action on metabolic processes.

We invite investigators to contribute to either original research paper or review articles focusing on tissue crosstalk, impact on insulin resistance and the pathogenesis of metabolic diseases in animal models and clinical settings. Special attention will be given to the release of circulating factors under physiological or stress conditions, such as exercise, fasting/feeding, diet-induced obesity, and circadian rhythms. Articles should also discuss the mechanisms by which the circulating factors can cause or contribute to the progression of insulin resistance, type 2 diabetes and cardiometabolic abnormalities.