PMID- 37812879
OWN - NLM
STAT- MEDLINE
DCOM- 20231030
LR  - 20231031
IS  - 2213-2317 (Electronic)
IS  - 2213-2317 (Linking)
VI  - 67
DP  - 2023 Nov
TI  - 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.
PG  - 102918
LID - S2213-2317(23)00319-1 [pii]
LID - 10.1016/j.redox.2023.102918 [doi]
LID - 102918
AB  - 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 
      2x20 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/m(2)/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 
      Akt(Ser437) and AS160(Thr642) were inconclusive, but there was good evidence for 
      increased IRS(Ser312) (41%; 3%, 95%), insulin-stimulated NFkappaB-DNA binding (46%; 
      3.4%, 105%), and basal PAK-1(Thr423)/2(Thr402) 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.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Peeters, W M
AU  - Peeters WM
AD  - Metabolic and Microvascular Laboratory, School of Sport, Exercise and Nutrition, 
      Massey University, Wellington, Auckland, New Zealand; School of Biomedical, 
      Nutritional and Sport Science, Newcastle University, United Kingdom.
FAU - Gram, M
AU  - Gram M
AD  - Metabolic and Microvascular Laboratory, School of Sport, Exercise and Nutrition, 
      Massey University, Wellington, Auckland, New Zealand.
FAU - Dias, G J
AU  - Dias GJ
AD  - Department of Anatomy, University of Otago, Dunedin, New Zealand.
FAU - Vissers, M C M
AU  - Vissers MCM
AD  - Centre for Free Radical Research, Department of Pathology and Biomedical Science, 
      University of Otago, Christchurch, New Zealand.
FAU - Hampton, M B
AU  - Hampton MB
AD  - Centre for Free Radical Research, Department of Pathology and Biomedical Science, 
      University of Otago, Christchurch, New Zealand.
FAU - Dickerhof, N
AU  - Dickerhof N
AD  - Centre for Free Radical Research, Department of Pathology and Biomedical Science, 
      University of Otago, Christchurch, New Zealand.
FAU - Bekhit, A E
AU  - Bekhit AE
AD  - Department of Food Sciences, University of Otago, Dunedin, New Zealand.
FAU - Black, M J
AU  - Black MJ
AD  - Metabolic and Microvascular Laboratory, School of Sport, Exercise and Nutrition, 
      Massey University, Wellington, Auckland, New Zealand.
FAU - Oxboll, J
AU  - Oxboll J
AD  - Metabolic and Microvascular Laboratory, School of Sport, Exercise and Nutrition, 
      Massey University, Wellington, Auckland, New Zealand.
FAU - Bayer, S
AU  - Bayer S
AD  - Centre for Free Radical Research, Department of Pathology and Biomedical Science, 
      University of Otago, Christchurch, New Zealand.
FAU - Dickens, M
AU  - Dickens M
AD  - School of Health Sciences, Massey University, Wellington, Auckland, New Zealand.
FAU - Vitzel, K
AU  - Vitzel K
AD  - School of Health Sciences, Massey University, Wellington, Auckland, New Zealand.
FAU - Sheard, P W
AU  - Sheard PW
AD  - Department of Physiology, University of Otago, Dunedin, New Zealand.
FAU - Danielson, K M
AU  - Danielson KM
AD  - Department of Anaesthesiology and Surgery, University of Otago, Wellington, New 
      Zealand.
FAU - Hodges, L D
AU  - Hodges LD
AD  - Metabolic and Microvascular Laboratory, School of Sport, Exercise and Nutrition, 
      Massey University, Wellington, Auckland, New Zealand.
FAU - Brond, J C
AU  - Brond JC
AD  - Department of Sports Science and Clinical Biomechanics, Faculty of Health 
      Sciences, University of Southern Denmark, Odense, Denmark.
FAU - Bond, J
AU  - Bond J
AD  - Metabolic and Microvascular Laboratory, School of Sport, Exercise and Nutrition, 
      Massey University, Wellington, Auckland, New Zealand.
FAU - Perry, B G
AU  - Perry BG
AD  - School of Health Sciences, Massey University, Wellington, Auckland, New Zealand.
FAU - Stoner, L
AU  - Stoner L
AD  - Department of Exercise and Sport Science, University of North Carolina, Chapel 
      Hill, USA.
FAU - Cornwall, J
AU  - Cornwall J
AD  - Centre for Early Learning in Medicine, University of Otago, Dunedin, New Zealand.
FAU - Rowlands, D S
AU  - Rowlands DS
AD  - Metabolic and Microvascular Laboratory, School of Sport, Exercise and Nutrition, 
      Massey University, Wellington, Auckland, New Zealand. Electronic address: 
      D.S.Rowlands@massey.ac.nz.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20231005
PL  - Netherlands
TA  - Redox Biol
JT  - Redox biology
JID - 101605639
RN  - IY9XDZ35W2 (Glucose)
RN  - K848JZ4886 (Cysteine)
RN  - 0 (Insulin)
RN  - 0 (Protein Isoforms)
RN  - 68238-35-7 (Keratins)
SB  - IM
MH  - Adult
MH  - Humans
MH  - Glucose/metabolism
MH  - *Insulin Resistance
MH  - Cysteine/metabolism
MH  - Pilot Projects
MH  - Insulin/metabolism
MH  - Muscle, Skeletal/metabolism
MH  - *Diabetes Mellitus, Type 2/metabolism
MH  - Protein Isoforms/metabolism
MH  - Dietary Supplements
MH  - Oxidation-Reduction
MH  - Keratins/metabolism/pharmacology
PMC - PMC10570009
OTO - NOTNLM
OT  - Glutathione
OT  - Keratin
OT  - Oxidative stress
OT  - Peroxiredoxin
OT  - Type-2 diabetes
OT  - whey
COIS- Declaration of competing interest We were unable to get the Elsevier online DOI 
      working, so this document covers declarations.
EDAT- 2023/10/10 00:42
MHDA- 2023/10/30 06:47
PMCR- 2023/10/05
CRDT- 2023/10/09 18:21
PHST- 2023/08/22 00:00 [received]
PHST- 2023/10/02 00:00 [accepted]
PHST- 2023/10/30 06:47 [medline]
PHST- 2023/10/10 00:42 [pubmed]
PHST- 2023/10/09 18:21 [entrez]
PHST- 2023/10/05 00:00 [pmc-release]
AID - S2213-2317(23)00319-1 [pii]
AID - 102918 [pii]
AID - 10.1016/j.redox.2023.102918 [doi]
PST - ppublish
SO  - Redox Biol. 2023 Nov;67:102918. doi: 10.1016/j.redox.2023.102918. Epub 2023 Oct 
      5.