The Role of Insulin Within the Socio-Psycho-Biological Framework in Type 2 Diabetes-A Perspective from Psychoneuroimmunology

Abstract

The interplay between socio-psychological factors and biological systems is pivotal in defining human health and disease, particularly in chronic non-communicable diseases. Recent advancements in psychoneuroimmunology and mitochondrial psychobiology have emphasized the significance of psychological factors as critical determinants of disease onset, progression, recurrence, and severity. These insights align with evolutionary biology, psychology, and psychiatry, highlighting the inherent social nature of humans. This study proposes a theory that expands insulin's role beyond traditional metabolic functions, incorporating it into the Mitochondrial Information Processing System (MIPS) and exploring it from an evolutionary medicine perspective to explore its function in processing psychological and social factors into biological responses. This narrative review comprises data from preclinical animal studies, longitudinal cohort studies, cross-sectional studies, machine learning analyses, and randomized controlled trials, and investigates the role of insulin in health and disease. The result is a proposal for a theoretical framework of insulin as a social substance within the socio-psycho-biological framework, emphasizing its extensive roles in health and disease. Type 2 Diabetes Mellitus (T2DM) with musculoskeletal disorders and neurodegeneration exemplifies this narrative. We suggest further research towards a comprehensive treatment protocol meeting evolutionary expectations, where incorporating psychosocial interventions plays an essential role. By supporting the concept of 'insulin resilience' and suggesting the use of heart rate variability to assess insulin resilience, we aim to provide an integrative approach to managing insulin levels and monitoring the effectiveness of interventions. This integrative strategy addresses broader socio-psychological factors, ultimately improving health outcomes for individuals with T2DM and musculoskeletal complications and neurodegeneration while providing new insights into the interplay between socio-psychological factors and biological systems in chronic diseases.

Keywords: evolutionary medicine; insulin; insulin resilience; insulin resistance; integrative health interventions; mitochondrial dynamics; mitochondrial information processing system; psychoneuroimmunology; psychosocial factors; type 2 diabetes mellitus with musculoskeletal disorders and neurodegeneration.

Figure 1

Evolutionary ancient vs. modern stressors and their impact on insulin (INS). Modern stressors activate the HPA and SAM axes, increasing glucocorticoids and catecholamines, leading to elevated glucose and INS demand. Chronic activation induces lipolysis, TLR activation, and meta-inflammation, contributing to hyperinsulinemia and INS resistance (IR).

Figure 2

Incorporation of Insulin into the Mitochondrial Information Processing System (MIPS). This figure illustrates the potential role of insulin (INS) within the Mitochondrial Information Processing System (MIPS) in response to psychosocial and evolutionary novel stressors. Using the MIPS model and an evolutionary perspective, we propose that INS functions as a socio-psycho-metabolic hormone that cooperates with mitochondria to mediate the sensing, integration, and signaling of these stressors. This cooperation might affect mitochondrial dynamics through pathways such as AKT and MAPK. Prolonged hyperinsulinemia, driven by chronic stress, may lead to receptor resistance, impacting mitochondrial function. This figure highlights the hypothesized relationship between psychosocial stress, insulin resistance, and the development of complications associated with Type 2 Diabetes Mellitus (T2DM), such as neurodegeneration and musculoskeletal disorders (MSDs). By positioning insulin as a central modulator working in cooperation with mitochondria in the MIPS framework, we propose that it plays a key role in integrating psychosocial and metabolic signals, ultimately influencing health outcomes.

Figure 3

Evidence-based interventions within the mitochondrial information processing (MIPS) framework can enhance insulin resilience, a newly proposed health outcome resulting from the improvement of psychosocial factors and the implementation of evolutionary interventions. This ultimately contributes to positive health outcomes in conditions such as Type 2 Diabetes Mellitus (T2DM) with musculoskeletal (MS) problems and subsequent Chronic Non-Communicable Diseases (CNCDs), where the occurrence of one chronic condition increases the likelihood of developing additional diseases over time. Heart Rate Variability (HRV) is proposed as an additional parameter in the diagnostic toolbox, alongside existing parameters.