Insulin resistance, selfish brain, and selfish immune system: an evolutionarily positively selected program used in chronic inflammatory diseases.

Rainer H Straub

doi:10.1186/ar4688

Abstract

Insulin resistance (IR) is a general phenomenon of many physiological states, disease states, and diseases. IR has been described in diabetes mellitus, obesity, infection, sepsis, trauma, painful states such as postoperative pain and migraine, schizophrenia, major depression, chronic mental stress, and others. In arthritis, abnormalities of glucose homeostasis were described in 1920; and in 1950 combined glucose and insulin tests unmistakably demonstrated IR. The phenomenon is now described in rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, polymyalgia rheumatica, and others. In chronic inflammatory diseases, cytokine-neutralizing strategies normalize insulin sensitivity. This paper delineates that IR is either based on inflammatory factors (activation of the immune/ repair system) or on the brain (mental activation via stress axes). Due to the selfishness of the immune system and the selfishness of the brain, both can induce IR independent of each other. Consequently, the immune system can block the brain (for example, by sickness behavior) and the brain can block the immune system (for example, stress-induced immune system alterations). Based on considerations of evolutionary medicine, it is discussed that obesity per se is not a disease. Obesity-related IR depends on provoking factors from either the immune system or the brain. Chronic inflammation and/or stress axis activation are thus needed for obesity-related IR. Due to redundant pathways in stimulating IR, a simple one factor-neutralizing strategy might help in chronic inflammatory diseases (inflammation is the key), but not in obesity-related IR. The new considerations towards IR are interrelated to the published theories of IR (thrifty genotype, thrifty phenotype, and others).

Highlights

In 1916, the diabetologist Elliott P Joslin recognized that ‘hyperglycemic situations appear after infectious diseases, painful conditions such as gall stones, and trauma’ [1]
insulin resistance’ (IR) was found in physiological states, disease states, and diseases such as diabetes mellitus, obesity, infection, sepsis, arthritis of different
IR is an unfavorable factor in chronic inflammatory disease (CID) because it supports the already activated immune system

Summary

Introduction

In 1916, the diabetologist Elliott P Joslin recognized that ‘hyperglycemic situations appear after infectious diseases, painful conditions such as gall stones, and trauma’ [1]. IR was found in physiological states, disease states, and diseases such as diabetes mellitus, obesity, infection, sepsis, arthritis of different When considering these diseases and disease states, one observes two major clusters of clinical entities that are linked to IR: inflammation with an activated immune/ repair system; and increased mental activation. There is a highly delicate system of hypothalamic regulation of satiety

Reference methods

Conclusions

Findings

Joslin EP