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

• Published in: Redox biology Vol. 67; p. 102918
• Main Authors: Peeters, W.M., Gram, M., Dias, G.J., Vissers, M.C.M., Hampton, M.B., Dickerhof, N., Bekhit, A.E., Black, M.J., Oxbøll, J., Bayer, S., Dickens, M., Vitzel, K., Sheard, P.W., Danielson, K.M., Hodges, L.D., Brønd, J.C., Bond, J., Perry, B.G., Stoner, L., Cornwall, J., Rowlands, D.S.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.11.2023; Elsevier
• Subjects: Glutathione; Keratin; Oxidative stress; Peroxiredoxin; Research Paper; Type-2 diabetes; whey; Type-2 diabetes; Peroxiredoxin; Keratin; Oxidative stress; whey; Glutathione
• ISSN: 2213-2317; 2213-2317
• DOI: 10.1016/j.redox.2023.102918

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. [Display omitted] •Keratin derived protein blended with whey (KDPWHE) enhanced glucose clearance.•On insulin stimulation, KDPWHE increased muscle blood flow and GLUT4 translocation.•Increased basal oxidised PRX2 with KDPWHE was attenuated with insulin stimulation.•Insulin sensitivity was associated with increased antioxidant expression (GPx1, SOD1).