PMID- 26517932
OWN - NLM
STAT- MEDLINE
DCOM- 20160831
LR  - 20211203
IS  - 1470-8752 (Electronic)
IS  - 0300-5127 (Linking)
VI  - 43
IP  - 5
DP  - 2015 Oct
TI  - The TRIB3 Q84R polymorphism, insulin resistance and related metabolic 
      alterations.
PG  - 1108-11
LID - 10.1042/BST20150115 [doi]
AB  - Insulin resistance is pathogenic for many prevalent disorders including type 2 
      diabetes mellitus (T2DM), cardiovascular disease (CVD), polycystic ovary 
      syndrome, non-alcoholic fatty liver disease, Alzheimer's and Parkinson's diseases 
      and several cancers. Unravelling molecular abnormalities of insulin resistance 
      may therefore pave the way for tackling such heavy weight on healthcare systems. 
      This review will be focused on studies addressing the role of genetic variability 
      of TRIB3, an inhibitor of insulin signalling at the AKT level on insulin 
      resistance and several related abnormalities. Studies carried out in several 
      cultured cells clearly report that the TRIB3 Q84R missense polymorphism, is a 
      gain-of-function amino acid substitution, with the Arg(84) variant being a 
      stronger inhibitor of insulin-mediated AKT activation as compared with the more 
      frequent Gln(84) variant. Given the key role of AKT in modulating not only 
      insulin signalling but also insulin secretion, it was not surprising that beta-cells 
      and human pancreatic islets carrying the Arg(84) variant showed also impaired 
      insulin secretion. Also, of note is that in human vein endothelial cells carrying 
      the Arg(84) variant showed a reduced insulin-induced nitric oxide release, an 
      established early atherosclerotic step. Accordingly with in vitro studies, 
      in vivo studies indicate that TRIB3 Arg(84) is associated with insulin 
      resistance, T2DM and several aspects of atherosclerosis, including overt CVD. In 
      all, several data indicate that the TRIB3 Arg(84) variant plays a role on several 
      aspects of glucose homoeostasis and atherosclerotic processes, thus unravelling 
      new molecular pathogenic mechanisms of highly prevalent disorders such as T2DM 
      and CVD.
CI  - (c) 2015 Authors; published by Portland Press Limited.
FAU - Prudente, Sabrina
AU  - Prudente S
AD  - Mendel Laboratory, IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni 
      Rotondo, Italy s.prudente@css-mendel.it Vincenzo.Trischitta@uniroma1.it.
FAU - Trischitta, Vincenzo
AU  - Trischitta V
AD  - Mendel Laboratory, IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni 
      Rotondo, Italy Research Unit of Diabetes and Endocrine Diseases, IRCCS Casa 
      Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy Department of 
      Experimental Medicine, Sapienza University, 00161 Rome, Italy 
      s.prudente@css-mendel.it Vincenzo.Trischitta@uniroma1.it.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - England
TA  - Biochem Soc Trans
JT  - Biochemical Society transactions
JID - 7506897
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (TRIB3 protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Amino Acid Substitution
MH  - Atherosclerosis/*genetics/metabolism
MH  - Cell Cycle Proteins/*genetics
MH  - Diabetes Mellitus, Type 2/*genetics/metabolism
MH  - Enzyme Activation
MH  - Humans
MH  - Insulin Resistance/*genetics
MH  - Mutation, Missense
MH  - *Polymorphism, Single Nucleotide
MH  - Protein Serine-Threonine Kinases/*antagonists & inhibitors/genetics
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Repressor Proteins/*genetics
OTO - NOTNLM
OT  - cardiovascular disease
OT  - insulin resistance
OT  - insulin signaling
OT  - type 2 diabetes
EDAT- 2015/11/01 06:00
MHDA- 2016/09/01 06:00
CRDT- 2015/10/31 06:00
PHST- 2015/10/31 06:00 [entrez]
PHST- 2015/11/01 06:00 [pubmed]
PHST- 2016/09/01 06:00 [medline]
AID - BST20150115 [pii]
AID - 10.1042/BST20150115 [doi]
PST - ppublish
SO  - Biochem Soc Trans. 2015 Oct;43(5):1108-11. doi: 10.1042/BST20150115.