PMID- 32798372
OWN - NLM
STAT- MEDLINE
DCOM- 20210701
LR  - 20210701
IS  - 1875-5305 (Electronic)
IS  - 0929-8665 (Linking)
VI  - 28
IP  - 3
DP  - 2021
TI  - Phosphorylated and O-GlcNAc Modified IRS-1 (Ser1101) and -2 (Ser1149) Contribute 
      to Human Diabetes Type II.
PG  - 333-339
LID - 10.2174/0929866527666200813210407 [doi]
AB  - BACKGROUND: The prevalence of the chronic metabolic disorder Type 2 diabetes 
      mellitus (T2DM) is increasing steadily, and has even turned into an epidemic in 
      some countries. T2DM results from defective responses to insulin and obesity is a 
      major factor behind insulin resistance in T2DM. Insulin receptor substrate (IRS) 
      proteins are adaptor proteins in the insulin receptor signalling pathway. The 
      insulin signalling is controlled through tyrosine phosphorylation of IRS-1 and 
      IRS-2, and dysregulation of IRS proteins signalling may lead to glucose 
      intolerance and eventually insulin resistance. OBJECTIVE: In this work, we 
      suggest that both glycosylation (O-GlcNAc modification) and phosphorylation of 
      IRS-1 and -2 are involved in the pathogenesis of T2DM. METHODS: Phosphorylation 
      and O-GlcNAc modifications (Ser1101 in IRS-1 and Ser1149 in IRS-2) proteins were 
      determined experimentally by sandwich ELISA with specific antibodies and with 
      bioinformatics tools. RESULTS: When IRS-1 (on Ser1101) and IRS-2 (Ser1149) become 
      glycosylated following an increase in UDP-GlcNAc pools, it may contribute to 
      insulin resistance. Whereas when the same (IRS-1 on Ser1101 and IRS-2 on Ser1149) 
      are phosphorylated, the insulin signalling is inhibited. DISCUSSION: In this work 
      OGlcNAc-modified proteins were specifically detected using O-Glc- NAc-specific 
      antibodies, suggesting that elevated levels of O-GlcNAc-modified proteins are 
      found, independently of their possible involvement in Advanced Glycation End 
      products (AGEs). CONCLUSION: This study suggests a mechanism, which is controlled 
      by posttranslational modifications, and may contribute to the pathogenesis of 
      type II diabetes.
CI  - Copyright(c) Bentham Science Publishers; For any queries, please email at 
      epub@benthamscience.net.
FAU - Kaleem, Afshan
AU  - Kaleem A
AD  - Department of Biotechnology, Lahore College for Women University, Lahore, Punjab 
      54000, Pakistan.
FAU - Javed, Sabahat
AU  - Javed S
AD  - Department of Biotechnology, Lahore College for Women University, Lahore, Punjab 
      54000, Pakistan.
FAU - Rehman, Nayab
AU  - Rehman N
AD  - Department of Biotechnology, Lahore College for Women University, Lahore, Punjab 
      54000, Pakistan.
FAU - Abdullah, Roheena
AU  - Abdullah R
AD  - Department of Biotechnology, Lahore College for Women University, Lahore, Punjab 
      54000, Pakistan.
FAU - Iqtedar, Mehwish
AU  - Iqtedar M
AD  - Department of Biotechnology, Lahore College for Women University, Lahore, Punjab 
      54000, Pakistan.
FAU - Aftab, Mohammad Nauman
AU  - Aftab MN
AD  - Institute of Industrial Biotechnology, Government College University, Lahore, 
      Pakistan.
FAU - Hoessli, Daniel C
AU  - Hoessli DC
AD  - Dr. Panjwani Center for Molecular Medicine and Drug Research, International 
      Center for Chemical and Biological Sciences, University of Karachi, Karachi, 
      Pakistan.
FAU - Haq, Ikram-Ul
AU  - Haq IU
AD  - Institute of Industrial Biotechnology, Government College University, Lahore, 
      Pakistan.
LA  - eng
GR  - 20-3989/HEC/
PT  - Journal Article
PL  - Netherlands
TA  - Protein Pept Lett
JT  - Protein and peptide letters
JID - 9441434
RN  - 0 (IRS1 protein, human)
RN  - 0 (Insulin)
RN  - 0 (Insulin Receptor Substrate Proteins)
SB  - IM
MH  - Diabetes Mellitus, Type 2/*metabolism
MH  - Female
MH  - Glycosylation
MH  - Humans
MH  - Insulin/*metabolism
MH  - Insulin Receptor Substrate Proteins/*metabolism
MH  - Male
MH  - Phosphorylation
MH  - *Signal Transduction
OTO - NOTNLM
OT  - Insulin receptor substrates
OT  - O-glycosylation
OT  - diabetes type II
OT  - insulin resistance
OT  - pathogenesis.
OT  - phosphorylation
EDAT- 2020/08/18 06:00
MHDA- 2021/07/02 06:00
CRDT- 2020/08/18 06:00
PHST- 2020/05/15 00:00 [received]
PHST- 2020/06/09 00:00 [revised]
PHST- 2020/06/11 00:00 [accepted]
PHST- 2020/08/18 06:00 [pubmed]
PHST- 2021/07/02 06:00 [medline]
PHST- 2020/08/18 06:00 [entrez]
AID - PPL-EPUB-109109 [pii]
AID - 10.2174/0929866527666200813210407 [doi]
PST - ppublish
SO  - Protein Pept Lett. 2021;28(3):333-339. doi: 10.2174/0929866527666200813210407.