PMID- 29291420
OWN - NLM
STAT- MEDLINE
DCOM- 20180213
LR  - 20180213
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 194
DP  - 2018 Feb 1
TI  - Vitamin C and E chronic supplementation differentially affect hepatic insulin 
      signaling in rats.
PG  - 196-204
LID - S0024-3205(17)30689-6 [pii]
LID - 10.1016/j.lfs.2017.12.039 [doi]
AB  - AIM: Vitamin C and vitamin E supplementations and their beneficial effects on 
      type 2 diabetes mellitus (T2DM) have been subjected to countless controversial 
      data. Hence, our aim is to investigate the hepatic molecular mechanisms of any 
      diabetic predisposing risk of the chronic administration of different doses of 
      vitamin E or vitamin C in rats. MAIN METHODS: The rats were supplemented with 
      different doses of vitamin C or vitamin E for eight months. KEY FINDINGS: Vitamin 
      C and vitamin E increased fasting blood glucose, insulin, and homeostasis model 
      assessment index for insulin resistance (HOMA). Vitamin C disrupted glucose 
      tolerance by attenuating upstream hepatic insulin action through impairing the 
      phosphorylation and activation of insulin receptor and its subsequent substrates; 
      however, vitamin E showed its effect downstream insulin receptor in the insulin 
      signaling pathway, reducing hepatic glucose transporter-2 (GLUT2) and 
      phosphorylated protein kinase (p-Akt). Moreover, both vitamins showed their 
      antioxidant capabilities [nuclear factor-erythroid-2-related factor 2 (Nrf2), 
      total and reduced glutathione] and their negative effect on Wnt pathway 
      [phosphorylated glycogen synthase kinase-3beta (p-GSK-3beta)], by altering the 
      previously mentioned parameters, inevitably leading to severe reduction of 
      reactive oxygen species (ROS) below the physiological levels. SIGNIFICANCE: In 
      conclusion, a detrimental effect of chronic antioxidant vitamins supplementation 
      was detected; leading to insulin resistance and impaired glucose tolerance 
      obviously through different mechanisms. Overall, these findings indicate that the 
      conventional view that vitamins promote health benefits and delay chronic 
      illnesses and aging should be modified or applied with caution.
CI  - Copyright (c) 2017. Published by Elsevier Inc.
FAU - Ali, Mennatallah A
AU  - Ali MA
AD  - Department of Pharmacology &Therapeutics, Faculty of Pharmacy and Drug 
      Manufacturing, Pharos University, Alexandria, Egypt. Electronic address: 
      mennaallah.ismail@pua.edu.eg.
FAU - Eid, Rania M H M
AU  - Eid RMHM
AD  - Department of Physiology, Faculty of Medicine, Aswan University, Egypt.
FAU - Hanafi, Mervat Y
AU  - Hanafi MY
AD  - Department of Biochemistry, Medical Research Institute, Alexandria University, 
      Alexandria, Egypt.
LA  - eng
PT  - Journal Article
DEP - 20171230
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Antioxidants)
RN  - 0 (Insulin)
RN  - 0 (Vitamins)
RN  - 1406-18-4 (Vitamin E)
RN  - IY9XDZ35W2 (Glucose)
RN  - PQ6CK8PD0R (Ascorbic Acid)
SB  - IM
MH  - Animals
MH  - Antioxidants/administration & dosage/*pharmacology
MH  - Ascorbic Acid/administration & dosage/*pharmacology
MH  - Glucose/metabolism
MH  - Insulin/*metabolism
MH  - Insulin Resistance
MH  - Liver/*drug effects/metabolism
MH  - Male
MH  - Oxidative Stress/drug effects
MH  - Rats
MH  - Rats, Wistar
MH  - Signal Transduction/*drug effects
MH  - Vitamin E/administration & dosage/*pharmacology
MH  - Vitamins/administration & dosage/*pharmacology
MH  - Wnt Signaling Pathway/drug effects
OTO - NOTNLM
OT  - GLUT2
OT  - Glutathione
OT  - Insulin resistance
OT  - Nrf2
OT  - Phosphorylated insulin receptor
OT  - UCP2
OT  - Wnt pathway
OT  - p-Akt
EDAT- 2018/01/02 06:00
MHDA- 2018/02/14 06:00
CRDT- 2018/01/02 06:00
PHST- 2017/08/31 00:00 [received]
PHST- 2017/12/19 00:00 [revised]
PHST- 2017/12/29 00:00 [accepted]
PHST- 2018/01/02 06:00 [pubmed]
PHST- 2018/02/14 06:00 [medline]
PHST- 2018/01/02 06:00 [entrez]
AID - S0024-3205(17)30689-6 [pii]
AID - 10.1016/j.lfs.2017.12.039 [doi]
PST - ppublish
SO  - Life Sci. 2018 Feb 1;194:196-204. doi: 10.1016/j.lfs.2017.12.039. Epub 2017 Dec 
      30.