PMID- 10364263
OWN - NLM
STAT- MEDLINE
DCOM- 19990715
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 25
DP  - 1999 Jun 18
TI  - Insulin receptor substrate 3 is not essential for growth or glucose homeostasis.
PG  - 18093-9
AB  - The insulin receptor substrates (IRS) 1 and 2 are required for normal growth and 
      glucose homeostasis in mice. To determine whether IRS-3, a recently cloned member
      of the IRS family, is also involved in the regulation of these, we have generated
      mice with a targeted disruption of the IRS-3 gene and characterized them.
      Compared with wild-type mice, the IRS-3-null mice showed normal body weight
      throughout development, normal blood glucose levels in the fed and fasted state
      and following an oral glucose bolus, and normal fed and fasted plasma insulin
      levels. IRS-3 is most abundant in adipocytes and is tyrosine-phosphorylated in
      response to insulin in these cells. Therefore, isolated adipocytes were analyzed 
      for changes in insulin effects. Insulin-stimulated glucose transport in the
      adipocytes from the IRS-3-null mice was the same as in wild-type cells. The
      extent of tyrosine phosphorylation of IRS-1/2 following insulin stimulation was
      similar in adipocytes from IRS-3-null and wild-type mice, and the insulin-induced
      association of tyrosine-phosphorylated IRS-1/2 with phosphatidylinositol 3-kinase
      and SHP-2 was not detectably increased by IRS-3 deficiency. Thus, IRS-3 was not
      essential for normal growth, glucose homeostasis, and glucose transport in
      adipocytes, and in its absence no significant compensatory augmentation of
      insulin signaling through IRS-1/2 was evident.
FAU - Liu, S C
AU  - Liu SC
AD  - Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire
      03755, USA.
FAU - Wang, Q
AU  - Wang Q
FAU - Lienhard, G E
AU  - Lienhard GE
FAU - Keller, S R
AU  - Keller SR
LA  - eng
GR  - DK42816/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Blood Glucose)
RN  - 0 (Insulin)
RN  - 0 (Insulin Receptor Substrate Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Irs3 protein, mouse)
RN  - 0 (Phosphoproteins)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 11)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 6)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatases)
RN  - EC 3.1.3.48 (Ptpn11 protein, mouse)
RN  - EC 3.1.3.48 (Ptpn6 protein, mouse)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Adipocytes/drug effects/metabolism
MH  - Animals
MH  - Biological Transport
MH  - Blood Glucose/*metabolism
MH  - Body Weight
MH  - Female
MH  - Gene Targeting
MH  - Glucose/metabolism
MH  - Homeostasis/genetics
MH  - Insulin/pharmacology
MH  - Insulin Receptor Substrate Proteins
MH  - Intracellular Signaling Peptides and Proteins
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphoproteins/*genetics/metabolism
MH  - Phosphorylation
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 11
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 6
MH  - Protein Tyrosine Phosphatases/metabolism
EDAT- 1999/06/11 00:00
MHDA- 1999/06/11 00:01
CRDT- 1999/06/11 00:00
PHST- 1999/06/11 00:00 [pubmed]
PHST- 1999/06/11 00:01 [medline]
PHST- 1999/06/11 00:00 [entrez]
AID - 10.1074/jbc.274.25.18093 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Jun 18;274(25):18093-9. doi: 10.1074/jbc.274.25.18093.