Discussion
hormesis, T2DM
INSULIN RESISTANCE, INSULIN SENSITIVITY
There was good evidence to suggest that the ingestion of the cysteine-rich keratin-derived combinatorial protein blend (KDPWHE) for 14 weeks by adults with T2DM produced a clinically relevant increase in whole-body glucose clearance rate (GCR), relative to a non-protein placebo control (CON), based on the mean effect size (24%) being comparable to pioglitazone + metformin intervention of similar duration [The GCR response following KDPWHE supplementation was supported mechanistically by association with good to very-good level evidence for enhanced nutrient-delivery phenotype and insulin sensitivity within the skeletal muscle – the largest tissue mass responsible for glucose disposal and metabolism [The good evidence for improved insulin-stimulated skeletal muscle microvascular blood flow (mBF) and for increased GLUT4 translocation provides for a candidate tissue-level mechanism responsible for the enhanced GCR, because tissue glucose delivery and uptake is partially regulated by insulin-stimulated mBF [The current data also provide the first indicative evidence to suggest a change in dietary protein pattern can modify insulin-stimulated sarcolemmal GLUT4 density in humans with T2DM. The increase in GLUT4 translocation with KDPWHE supplementation was accompanied with good evidence for a substantially higher IRSAt study onset, we believed that the KDPWHE would increase GSH synthesis, potentially increasing its endogenous antioxidant tissue levels to boost cellular reducing capacity and improve insulin sensitivity, as indicated in prior literature by association [The small-moderate change in basal redox state with KDPWHE may have accumulated over time to drive a comparatively greater adaptive response (hormesis) [Several limitations should be noted. The study was an exploratory pilot with the motivation to study based by the only prior evidence of any possible glycaemic effect from a mouse trial and from interpolation of a role for redox and tissue glutathione depletion in insulin resistance [Our insulin-sensitivity analysis focus was on traditional and established regulatory processes of relatively macro-level redox markers. However, a myriad of other possible evolutionarily conserved post-translational protein modifications at redox sensitive protein sites may be functional in insulin-signalling or sensitivity processes [