PMID- 12409500
OWN - NLM
STAT- MEDLINE
DCOM- 20030606
LR  - 20220216
IS  - 0022-0949 (Print)
IS  - 0022-0949 (Linking)
VI  - 205
IP  - Pt 23
DP  - 2002 Dec
TI  - Gliclazide increases insulin receptor tyrosine phosphorylation but not p38 
      phosphorylation in insulin-resistant skeletal muscle cells.
PG  - 3739-46
AB  - Sulfonylurea drugs are used in the treatment of type 2 diabetes. The mechanism of 
      action of sulfonylureas is to release insulin from pancreatic cells and they have 
      been proposed to act on insulin-sensitive tissues to enhance glucose uptake. The 
      goal of the present study was to test the hypothesis that gliclazide, a 
      second-generation sulfonylurea, could enhance insulin signaling in 
      insulin-resistant skeletal muscle cells. We demonstrated that gliclazide enhanced 
      insulin-stimulated insulin receptor tyrosine phosphorylation in insulin-resistant 
      skeletal muscle cells. Although insulin receptor substrate-1 tyrosine 
      phosphorylation was unaffected by gliclazide treatment, phosphatidylinositol 
      3-kinase activity was partially restored by treatment with gliclazide. No 
      increase in 2-deoxyglucose uptake in insulin-resistant cells by treatment with 
      gliclazide was observed. Further investigations into the mitogen-activated 
      protein kinase (MAPK) pathway revealed that insulin-stimulated p38 
      phosphorylation was impaired, as compared with extracellular-signal-regulated 
      kinase (ERK) and c-Jun N-terminal kinase (JNK), which were phosphorylated 
      normally in insulin-resistant cells. Treatment with gliclazide could not restore 
      p38 phosphorylation in insulin-resistant cells. We propose that gliclazide can 
      regulate part of the insulin signaling in insulin-resistant skeletal muscle, and 
      p38 could be a potential therapeutic target for glucose uptake to treat insulin 
      resistance.
FAU - Kumar, Naresh
AU  - Kumar N
AD  - Department of Biotechnology, National Institute of Pharmaceutical Education and 
      Research, Punjab, India.
FAU - Dey, Chinmoy S
AU  - Dey CS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Exp Biol
JT  - The Journal of experimental biology
JID - 0243705
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Imidazoles)
RN  - 0 (Insulin)
RN  - 0 (Pyridines)
RN  - 42HK56048U (Tyrosine)
RN  - 9G2MP84A8W (Deoxyglucose)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.10.1 (Receptor, Insulin)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 4)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
RN  - G4PX8C4HKV (Gliclazide)
RN  - OU13V1EYWQ (SB 203580)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Deoxyglucose/metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - Gliclazide/*pharmacology
MH  - Hypoglycemic Agents/pharmacology
MH  - Imidazoles/pharmacology
MH  - Insulin/pharmacology
MH  - *Insulin Resistance
MH  - *JNK Mitogen-Activated Protein Kinases
MH  - MAP Kinase Kinase 4
MH  - Mice
MH  - Mitogen-Activated Protein Kinase Kinases/metabolism
MH  - Mitogen-Activated Protein Kinases/antagonists & inhibitors/*metabolism
MH  - Muscle, Skeletal/drug effects/*metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphorylation
MH  - Pyridines/pharmacology
MH  - Receptor, Insulin/*chemistry
MH  - Signal Transduction
MH  - Tyrosine/*metabolism
MH  - p38 Mitogen-Activated Protein Kinases
EDAT- 2002/11/01 04:00
MHDA- 2003/06/07 05:00
CRDT- 2002/11/01 04:00
PHST- 2002/11/01 04:00 [pubmed]
PHST- 2003/06/07 05:00 [medline]
PHST- 2002/11/01 04:00 [entrez]
AID - 10.1242/jeb.205.23.3739 [doi]
PST - ppublish
SO  - J Exp Biol. 2002 Dec;205(Pt 23):3739-46. doi: 10.1242/jeb.205.23.3739.