PMID- 14998989
OWN - NLM
STAT- MEDLINE
DCOM- 20040615
LR  - 20220408
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 279
IP  - 19
DP  - 2004 May 7
TI  - Effects of rexinoids on glucose transport and insulin-mediated signaling in 
      skeletal muscles of diabetic (db/db) mice.
PG  - 19721-31
AB  - Rexinoids and thiazolidinediones (TZDs) are two classes of nuclear receptor 
      ligands that induce insulin sensitization in diabetic rodents. TZDs are 
      peroxisome proliferator-activated receptor gamma (PPARgamma) activators, whereas 
      rexinoids are selective ligands for the retinoid X receptors (RXRs). Activation 
      of both the insulin receptor substrates (IRSs)/Akt and the c-Cbl-associated 
      protein (CAP)/c-Cbl pathways are important in regulating insulin-stimulated 
      glucose transport. We have compared the effects of a rexinoid (LG268) and a TZD 
      (rosiglitazone) on these two signal pathways in skeletal muscle of diabetic 
      (db/db) mice. The results we have obtained show that treatment of db/db mice with 
      either LG268 or rosiglitazone for 2 weeks results in a significant increase in 
      insulin-stimulated glucose transport activity in skeletal muscle. Treatment with 
      LG268 increases insulin-stimulated IRS-1 tyrosine phosphorylation and Akt 
      phosphorylation in skeletal muscle without affecting the activity of the 
      CAP/c-Cbl pathway. In contrast, rosiglitazone increases the levels of CAP 
      expression and insulin-stimulated c-Cbl phosphorylation without affecting the 
      IRS-1/Akt pathway. The effects of LG268 on the IRS-1/Akt pathway were associated 
      with a decrease in the level of IRS-1 Ser(307) phosphorylation. Taken together, 
      these data suggest that rexinoids improve insulin sensitivity via changes in 
      skeletal muscle metabolism that are distinct from those induced by TZDs. 
      Rexinoids represent a novel class of insulin sensitizers with potential 
      applications in the treatment of insulin resistance.
FAU - Shen, Qi
AU  - Shen Q
AD  - Department of Integrative Biology and Pharmacology, University of Texas Medical 
      School, 6431 Fannin Street, Houston, TX 77225, USA.
FAU - Cline, Gary W
AU  - Cline GW
FAU - Shulman, Gerald I
AU  - Shulman GI
FAU - Leibowitz, Mark D
AU  - Leibowitz MD
FAU - Davies, Peter J A
AU  - Davies PJ
LA  - eng
GR  - R01 DK040936/DK/NIDDK NIH HHS/United States
GR  - DK 60045/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20040302
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Acyl Coenzyme A)
RN  - 0 (Anticholesteremic Agents)
RN  - 0 (Insulin)
RN  - 0 (LG 268)
RN  - 0 (Ligands)
RN  - 0 (Organic Chemicals)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Thiazolidinediones)
RN  - 0 (Transcription Factors)
RN  - 0 (Triglycerides)
RN  - 05V02F2KDG (Rosiglitazone)
RN  - 42HK56048U (Tyrosine)
RN  - 9G2MP84A8W (Deoxyglucose)
RN  - EC 2.3.2.27 (Proto-Oncogene Proteins c-cbl)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.7.10.1 (Receptor, Insulin)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 6.- (Ligases)
RN  - EC 6.3.2.- (Cbl protein, mouse)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Acyl Coenzyme A/metabolism
MH  - Animals
MH  - Anticholesteremic Agents/*pharmacology
MH  - Biological Transport
MH  - Blotting, Western
MH  - Body Weight/drug effects
MH  - Cattle
MH  - Deoxyglucose/metabolism
MH  - Diabetes Mellitus, Experimental
MH  - Glucose/*metabolism
MH  - Insulin/*metabolism
MH  - Insulin Resistance
MH  - Ligands
MH  - Ligases/metabolism
MH  - Mice
MH  - Muscle, Skeletal/drug effects/*metabolism
MH  - Muscles/metabolism
MH  - Organic Chemicals
MH  - Phosphorylation
MH  - Precipitin Tests
MH  - *Protein Serine-Threonine Kinases
MH  - Proto-Oncogene Proteins/metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Proto-Oncogene Proteins c-cbl
MH  - RNA, Messenger/metabolism
MH  - Receptor, Insulin/metabolism
MH  - Receptors, Cytoplasmic and Nuclear/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Rosiglitazone
MH  - Signal Transduction
MH  - Thiazolidinediones/*pharmacology
MH  - Transcription Factors/metabolism
MH  - Triglycerides/blood
MH  - Tyrosine/metabolism
MH  - *Ubiquitin-Protein Ligases
EDAT- 2004/03/05 05:00
MHDA- 2004/06/16 05:00
CRDT- 2004/03/05 05:00
PHST- 2004/03/05 05:00 [pubmed]
PHST- 2004/06/16 05:00 [medline]
PHST- 2004/03/05 05:00 [entrez]
AID - S0021-9258(20)67081-8 [pii]
AID - 10.1074/jbc.M311729200 [doi]
PST - ppublish
SO  - J Biol Chem. 2004 May 7;279(19):19721-31. doi: 10.1074/jbc.M311729200. Epub 2004 
      Mar 2.