PMID- 19924153
OWN - NLM
STAT- MEDLINE
DCOM- 20100202
LR  - 20211203
IS  - 1759-5037 (Electronic)
IS  - 1759-5029 (Linking)
VI  - 5
IP  - 12
DP  - 2009 Dec
TI  - Insulin signaling regulating genes: effect on T2DM and cardiovascular risk.
PG  - 682-93
LID - 10.1038/nrendo.2009.215 [doi]
AB  - Type 2 diabetes mellitus (T2DM) is a complex disorder that has a heterogeneous 
      genetic and environmental background. In this Review, we discuss the role of 
      relatively infrequent polymorphisms of genes that regulate insulin signaling 
      (including the K121Q polymorphism of ENPP1, the G972R polymorphism of IRS1 and 
      the Q84R polymorphism of TRIB3) in T2DM and other conditions related to insulin 
      resistance. The biological relevance of these three polymorphisms has been very 
      thoroughly characterized both in vitro and in vivo and the available data 
      indicate that they all affect insulin signaling and action as well as insulin 
      secretion. They also affect insulin-mediated regulation of endothelial cell 
      function. In addition, several reports indicate that the effects of all three 
      polymorphisms on the risk of T2DM and cardiovascular diseases related to insulin 
      resistance depend on the clinical features of the individual, including their 
      body weight and age at disease onset. Thus, these polymorphisms might be used to 
      demonstrate how difficult it is to ascertain the contribution of relatively 
      infrequent genetic variants with heterogeneous effects on disease susceptibility. 
      Unraveling the role of such variants might be facilitated by improving disease 
      definition and focusing on specific subsets of patients.
FAU - Prudente, Sabrina
AU  - Prudente S
AD  - IRCCS Casa Sollievo della Sofferenza, Mendel Institute, Rome, Italy.
FAU - Morini, Eleonora
AU  - Morini E
FAU - Trischitta, Vincenzo
AU  - Trischitta V
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - England
TA  - Nat Rev Endocrinol
JT  - Nature reviews. Endocrinology
JID - 101500078
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (IRS1 protein, human)
RN  - 0 (Insulin)
RN  - 0 (Insulin Receptor Substrate Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (TRIB3 protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 3.1.4.- (Phosphoric Diester Hydrolases)
RN  - EC 3.1.4.1 (ectonucleotide pyrophosphatase phosphodiesterase 1)
RN  - EC 3.6.1.- (Pyrophosphatases)
SB  - IM
MH  - Cardiovascular Diseases/*metabolism
MH  - Cell Cycle Proteins/genetics
MH  - Diabetes Mellitus, Type 2/*metabolism
MH  - Humans
MH  - Insulin/*metabolism
MH  - Insulin Receptor Substrate Proteins/genetics
MH  - Phosphoric Diester Hydrolases/genetics
MH  - Protein Serine-Threonine Kinases/genetics
MH  - Pyrophosphatases/genetics
MH  - Repressor Proteins/genetics
MH  - Risk Factors
MH  - *Signal Transduction/genetics/physiology
RF  - 149
EDAT- 2009/11/20 06:00
MHDA- 2010/02/03 06:00
CRDT- 2009/11/20 06:00
PHST- 2009/11/20 06:00 [entrez]
PHST- 2009/11/20 06:00 [pubmed]
PHST- 2010/02/03 06:00 [medline]
AID - nrendo.2009.215 [pii]
AID - 10.1038/nrendo.2009.215 [doi]
PST - ppublish
SO  - Nat Rev Endocrinol. 2009 Dec;5(12):682-93. doi: 10.1038/nrendo.2009.215.