Insulin resistance: The central node of convergence between unfolded protein response, diabetes, and cancer - PubMed
7 days ago
- #Cancer
- #Insulin Resistance
- #Metabolic Disease
- Modern lifestyle patterns, such as high-calorie diets and sedentary behavior, contribute to obesity, insulin resistance (IR), and type 2 diabetes (T2D).
- Prolonged stress on pancreatic β-cells leads to dysfunction and chronic hyperglycemia.
- IR and its metabolic effects (hyperinsulinemia, hyperglycemia, dyslipidemia, inflammation) are linked to increased cancer risk in various organs.
- Key molecular mediators of cancer progression include aberrant insulin/IGF signaling, oxidative stress, inflammatory cytokines, and metabolic reprogramming.
- Endoplasmic reticulum (ER) and mitochondrial dysfunction, particularly via mitochondria-associated membranes (MAMs), play a critical role in IR.
- ER stress triggers the unfolded protein response (UPR), which, when dysregulated, contributes to metabolic and cellular dysfunction.
- Disrupted MAM integrity affects calcium signaling, mitochondrial metabolism, and ER-mitochondria crosstalk, worsening IR in multiple tissues.
- UPR dysregulation and MAM perturbations form a mechanistic link between IR, T2D, and cancer.
- Therapeutic strategies targeting ER stress, MAM integrity, and UPR signaling may improve insulin sensitivity and reduce metabolic and oncogenic risks.