Hormonal
Obesity and type 2 diabetes are characterized by impaired insulin-stimulated PI3K activity and downstream signaling (specifically AS160 phosphorylation and PKCλ/ζ activation) in skeletal muscle, leading to defective GLUT4 translocation and insulin resistance.
In obesity and type 2 diabetes, your muscles' ability to respond to insulin is blunted because the internal signaling chain (PI3K, AS160, PKC) is disrupted, preventing glucose transporters from moving to the cell surface. This is a signaling defect, not necessarily a lack of transporters. Weight loss and specific medications (like TZDs) can help restore this signaling.
Indeed, insulin-stimulated PI3K activity decreases in skeletal muscle of type 2 diabetic subjects [8,22], providing evidence for a defect in insulin signaling that could contribute to impaired Glut4 translocation and insulin resistance.
Why this rating
The paper is a review citing multiple human studies, transgenic mouse models, and biochemical assays, though it acknowledges some conflicting data regarding Akt.
Source
Molecular Mechanism of Insulin Resistance in Obesity and Type 2 Diabetes
Kang‐Duk Choi et al. · The Korean Journal of Internal Medicine · 2010
DOI 10.3904/kjim.2010.25.2.119
More from this paper
- Lifestyle interventions, specifically very low calorie diets (VLCD) leading to significant weight loss, can reverse defects in insulin signaling (PI3K, AS160, PKCλ/ζ) and improve insulin sensitivity in obese nondiabetic individuals.Good
- Thiazolidinediones (TZDs) improve insulin sensitivity primarily by reducing intramyocellular lipids and diacylglycerol, thereby reducing PKC activation, rather than directly enhancing insulin signaling pathways like PI3K/Akt in all patients.Moderate
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