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Changes in Cells Associated with Insulin Resistance
by Leszek Szablewski
Chair and Department of General Biology and Parasitology, Medical University of Warsaw, Chałubińskiego Str. 5, 02-004 Warsaw, Poland
Int. J. Mol. Sci. 2024, 25(4), 2397; https://doi.org/10.3390/ijms25042397
Submission received: 6 January 2024 / Revised: 10 February 2024 / Accepted: 14 February 2024 / Published: 18 February 2024

Abstract
Insulin is a polypeptide hormone synthesized and secreted by pancreatic β-cells. It plays an important role as a metabolic hormone. Insulin influences the metabolism of glucose, regulating plasma glucose levels and stimulating glucose storage in organs such as the liver, muscles and adipose tissue. It is involved in fat metabolism, increasing the storage of triglycerides and decreasing lipolysis. Ketone body metabolism also depends on insulin action, as insulin reduces ketone body concentrations and influences protein metabolism. It increases nitrogen retention, facilitates the transport of amino acids into cells and increases the synthesis of proteins. Insulin also inhibits protein breakdown and is involved in cellular growth and proliferation. On the other hand, defects in the intracellular signaling pathways of insulin may cause several disturbances in human metabolism, resulting in several chronic diseases. Insulin resistance, also known as impaired insulin sensitivity, is due to the decreased reaction of insulin signaling for glucose levels, seen when glucose use in response to an adequate concentration of insulin is impaired. Insulin resistance may cause, for example, increased plasma insulin levels. That state, called hyperinsulinemia, impairs metabolic processes and is observed in patients with type 2 diabetes mellitus and obesity. Hyperinsulinemia may increase the risk of initiation, progression and metastasis of several cancers and may cause poor cancer outcomes. Insulin resistance is a health problem worldwide; therefore, mechanisms of insulin resistance, causes and types of insulin resistance and strategies against insulin resistance are described in this review. Attention is also paid to factors that are associated with the development of insulin resistance, the main and characteristic symptoms of particular syndromes, plus other aspects of severe insulin resistance. This review mainly focuses on the description and analysis of changes in cells due to insulin resistance.

8. Conclusions and Perspectives
Insulin resistance, which reduces the responsiveness of cells and tissues to insulin, may be due to both genetic and environmental factors. It is associated with several pathologies and diseases, such as type 2 diabetes mellitus, polycystic ovary syndrome, glucose intolerance, hypertension, metabolic syndrome, cancers, obesity and so on. Severe insulin resistance is involved in clinical syndromes, such as Type A, Type B, Type C, HAIR-AN, Rabson–Mendenhall, leprechaunism and lipodystrophies. The prevalence of obesity and T2DM has increased dramatically worldwide, and individuals with these pathologies are at a higher risk of cancer and other diseases.
Different interactions and distinct molecular, cellular and physiological mechanisms contribute to the relationship between insulin resistance and observed metabolic dysfunctions. Unfortunately, these interactions remain unknown; however, significant progress has been made in understanding the associations between metabolic dysfunctions and severe insulin resistance. Therefore, these associations, mechanisms and interactions need further investigation. Understanding of insulin signaling and insulin resistance will stimulate new therapy designs, including gene therapies and new drugs.

6. Therapeutic Strategies for Insulin Resistance
Insulin resistance is associated with metabolic disturbances such as T2DM, metabolic syndrome, lipid abnormalities and hepatic derangements. There are suggested treatment strategies against insulin resistance. A sedentary lifestyle and the increased prevalence of obesity contribute to the development of insulin resistance and its consequences. Modifications to lifestyle focused on the reduction of calories and weight as well as increased physical activity are suggested as important factors against insulin resistance [3,232,233]. Suggested proposals include physical activity daily for 30 min and a suitable diet for maintaining a healthy weight, for example, the Mediterranean diet. In the case of severe hypertriglyceridemia, a very-low-fat diet may be appropriate [34]. Exercise can improve skeletal muscle insulin resistance [234]. There are several other strategies in insulin resistance prevention, such as using nature-derived compounds.

It increases nitrogen retention, facilitates the transport of amino acids into cells and increases the synthesis of proteins. Insulin also inhibits protein breakdown and is involved in cellular growth and proliferation. On the other hand, defects in the intracellular signaling pathways of insulin may cause several disturbances in human metabolism, resulting in several chronic diseases. Insulin resistance, also known as impaired insulin sensitivity, is due to the decreased reaction of insulin signaling for glucose levels, seen when glucose use in response to an adequate concentration of insulin is impaired. Insulin resistance may cause, for example, increased plasma insulin levels. That state, called hyperinsulinemia, impairs metabolic processes and is observed in patients with type 2 diabetes mellitus and obesity. Hyperinsulinemia may increase the risk of initiation, progression and metastasis of several cancers and may cause poor cancer outcomes.