A Review on Molecular Basis of the Role of Psychological Stress in the Development and Progression of Type 1 and Type 2 Diabetes Mellitus

Abstract

Prolonged stress has long been shown to have major effects on the development of both type of 
diabetes mellitus, type 1 and type 2. This paper reviews the interrelationship between stress and 
diabetes. Chronic physical or emotional stress can activate the Hypothalamus-pituitary-adrenal (HPA) 
axis to induce production of the stress hormone glucocorticoids. Glucocorticoids cause abrupt thymus 
involution and result in a failure or breakdown in immunological tolerance. As a result of breakdown in 
immunological tolerance autoreactive T-cells are escaped from thymus microenvironment which 
ensures self/non-self education and selection of mature T-cells before being exported to the periphery. 
Though regulatory T-cells (Treg) are present in the circulation, they are unable to suppress the 
autoreative T-cells from initiating the destruction of β-cells and the subsequent development of 
autoimmune type 1 diabetes. The destruction of β-cells can be mediated by various mechanisms 
including Fas-FasL, perforin/granzymes, reactive oxygen species, and cytokines (e.g., IL- 1β, IFN-γ). 
Oxidative stress leads to development of type 2 diabetes either by the activation of multiple stress
sensitive serine/threonine (Ser/Thr) kinase signaling cascades such as c-Jun NH2-terminal kinase (JNK) 
pathway resulting in insulin resistance and/or by causing defect in insulin gene expression due to the 
loss of at least two critical proteins {pancreatic and duodenal homeobox factor-1 (PDX-1) and 
musculoaponeurotic fibrosarcoma oncogene homolog A (MafA)} that activate the insulin promoter.