From the Research
Insulin resistance occurs when cells in the body become less responsive to insulin, preventing efficient glucose uptake, primarily due to defects in the insulin signaling pathway, as described in the most recent study 1. The primary mechanism involves defects in the insulin signaling pathway, particularly at the insulin receptor and post-receptor levels. When insulin binds to its receptor, it normally triggers a cascade of intracellular events including phosphorylation of insulin receptor substrates (IRS) and activation of phosphatidylinositol 3-kinase (PI3K), which ultimately leads to glucose transporter 4 (GLUT4) translocation to the cell membrane for glucose uptake. In insulin resistance, this pathway becomes impaired due to several factors including:
- Lipid accumulation in tissues (particularly intramuscular and liver fat)
- Chronic inflammation with increased cytokines like TNF-α and IL-6
- Oxidative stress
- Mitochondrial dysfunction
- Endoplasmic reticulum stress These factors lead to serine/threonine phosphorylation of IRS proteins rather than tyrosine phosphorylation, inhibiting the normal insulin signaling cascade. Additionally, genetic factors, obesity, physical inactivity, and certain medications can contribute to insulin resistance by exacerbating these cellular mechanisms, as supported by studies 2, 3, 4. The body compensates by producing more insulin (hyperinsulinemia), but eventually this compensation fails, potentially leading to type 2 diabetes, and is also associated with an increased risk of cancer, as suggested by recent research 5.