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    Changes to insulin sensitivity in glucose clearance systems and redox following dietary supplementation with a novel cysteine-rich protein: A pilot randomized controlled trial in humans with type-2 diabetes.
    (Elsevier B.V, 2023-10-07) Peeters WM; Gram M; Dias GJ; Vissers MCM; Hampton MB; Dickerhof N; Bekhit AE; Black MJ; Oxbøll J; Bayer S; Dickens M; Vitzel K; Sheard PW; Danielson KM; Hodges LD; Brønd JC; Bond J; Perry BG; Stoner L; Cornwall J; Rowlands DS
    We recently developed a novel keratin-derived protein (KDP) rich in cysteine, glycine, and arginine, with the potential to alter tissue redox status and insulin sensitivity. The KDP was tested in 35 human adults with type-2 diabetes mellitus (T2DM) in a 14-wk randomised controlled pilot trial comprising three 2×20 g supplemental protein/day arms: KDP-whey (KDPWHE), whey (WHEY), non-protein isocaloric control (CON), with standardised exercise. Outcomes were measured morning fasted and following insulin-stimulation (80 mU/m2/min hyperinsulinaemic-isoglycaemic clamp). With KDPWHE supplementation there was good and very-good evidence for moderate-sized increases in insulin-stimulated glucose clearance rate (GCR; 26%; 90% confidence limits, CL 2%, 49%) and skeletal-muscle microvascular blood flow (46%; 16%, 83%), respectively, and good evidence for increased insulin-stimulated sarcoplasmic GLUT4 translocation (18%; 0%, 39%) vs CON. In contrast, WHEY did not effect GCR (-2%; -25%, 21%) and attenuated HbA1c lowering (14%; 5%, 24%) vs CON. KDPWHE effects on basal glutathione in erythrocytes and skeletal muscle were unclear, but in muscle there was very-good evidence for large increases in oxidised peroxiredoxin isoform 2 (oxiPRX2) (19%; 2.2%, 35%) and good evidence for lower GPx1 concentrations (-40%; -4.3%, -63%) vs CON; insulin stimulation, however, attenuated the basal oxiPRX2 response (4%; -16%, 24%), and increased GPx1 (39%; -5%, 101%) and SOD1 (26%; -3%, 60%) protein expression. Effects of KDPWHE on oxiPRX3 and NRF2 content, phosphorylation of capillary eNOS and insulin-signalling proteins upstream of GLUT4 translocation AktSer437 and AS160Thr642 were inconclusive, but there was good evidence for increased IRSSer312 (41%; 3%, 95%), insulin-stimulated NFκB-DNA binding (46%; 3.4%, 105%), and basal PAK-1Thr423/2Thr402 phosphorylation (143%; 66%, 257%) vs WHEY. Our findings provide good evidence to suggest that dietary supplementation with a novel edible keratin protein in humans with T2DM may increase glucose clearance and modify skeletal-muscle tissue redox and insulin sensitivity within systems involving peroxiredoxins, antioxidant expression, and glucose uptake.
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    The physiological effects of nutritional thiol supplementation : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Sport and Exercise Science at Massey University, Manawatu, New Zealand
    (Massey University, 2018) McLeay, Yanita Dawn
    Endogenous antioxidant defence systems are largely comprised of thiol antioxidants and antioxidant enzymes. Keratin protein, being high in cysteic acid, has potential to improve antioxidant status via generation of several thiol antioxidants. Common dietary antioxidants are often used by athletes aiming to reduce oxidative stress, which in turn can improve exercise performance. However, whilst studies into their action against oxidative stress are positive, the subsequent effect on exercise performance is less so. In addition to having little effect on acute performance, their non-­‐specific ROS-­‐targeting mechanisms may also blunt important adaptation signalling pathways. It has been proposed that improving endogenous defence systems may be of greater benefit to athletic performance, thus keratin may be an alternative to dietary antioxidant supplementation. The first study within this thesis found acute keratin supplementation to improve plasma total thiol content, while longer term supplementation increased lean body mass significantly more than casein protein. Study two suggested one week of keratin vs. taurine supplementation did not affect plasma total thiol content, while study three found that despite no significant effects on serum total thiol content, taurine improved muscle recovery following eccentric-­‐induced muscle damage compared to a placebo. In summary, findings from this thesis suggest keratin may be a useful supplement for athletes wanting to maintain or gain lean body mass. This suggests implications for the use of keratin beyond athletes, potentially benefiting other population groups including the elderly and the sick. Results also suggest that supplementing with taurine following resistance exercise involving eccentric actions may improve recovery and subsequent performance. This research sets a platform for further investigation into the use of keratin and thiols for various areas of sporting performance.