PMID- 16713429
OWN - NLM
STAT- MEDLINE
DCOM- 20060712
LR  - 20131121
IS  - 0026-0495 (Print)
IS  - 0026-0495 (Linking)
VI  - 55
IP  - 6
DP  - 2006 Jun
TI  - Gliclazide protects 3T3L1 adipocytes against insulin resistance induced by 
      hydrogen peroxide with restoration of GLUT4 translocation.
PG  - 722-30
AB  - Increased oxidative stress under hyperglycemia may contribute to progressive 
      deterioration of peripheral insulin sensitivity. In this study, we investigated 
      whether gliclazide, a second-generation sulfonylurea, can protect 3T3L1 
      adipocytes from insulin resistance induced by oxidative stress, and whether 
      gliclazide can restore insulin-stimulated glucose transporter 4 (GLUT4) 
      translocation under oxidative stress. We incubated 3T3L1 adipocytes in hydrogen 
      peroxide to produce oxidative stress, then administered various concentrations of 
      gliclazide, N-acetylcystein (NAC), or glibenclamide. Cells treated with these 
      drugs were next exposed to insulin, subsequent glucose uptake was measured, and 
      the insulin-stimulated GLUT4 translocation was monitored in living cells. We 
      found that hydrogen peroxide treatment alone suppressed glucose uptake by insulin 
      stimulation to 65.9%+/-7.8% of the corresponding controls (P<.01). However, 
      addition of 0.1 to 10 micromol/L gliclazide to hydrogen peroxide-treated cells 
      dose-dependently restored glucose uptake, with 5 micromol/L gliclazide 
      significantly restoring glucose uptake to 93.3+/-6.6% (P<.01) even under hydrogen 
      peroxide. Treatment with the known anti-oxidant NAC also dose-dependently (0.1-10 
      mmol/L) restored insulin-induced glucose uptake in the presence of hydrogen 
      peroxide. However, glibenclamide (0.1-10 micromol/L), another second-generation 
      sulfonylurea, failed to improve glucose uptake. Similarly, treatment with 5 
      micromol/L gliclazide or 10 mmol/L NAC significantly overcome the reduction in 
      insulin-stimulated GLUT4 translocation by hydrogen peroxide (P<.01), whereas 5 
      micromol/L glibenclamide did not. Therefore our data regarding gliclazide further 
      characterize its mechanism of hypoglycemic effect: the observed improvements in 
      insulin sensitivity and in GLUT4 translocation indicate that gliclazide counters 
      the hydrogen peroxide-induced insulin resistance in 3T3L1 adipocytes and also 
      would further augment the hypoglycemic effect of this drug as insulinotropic 
      sulfonylurea.
FAU - Shimoyama, Tatsuhiro
AU  - Shimoyama T
AD  - Third Department of Internal Medicine, Kyorin University School of Medicine, 
      Mitaka, Tokyo 181-8611, Japan.
FAU - Yamaguchi, Shinya
AU  - Yamaguchi S
FAU - Takahashi, Kazuto
AU  - Takahashi K
FAU - Katsuta, Hidenori
AU  - Katsuta H
FAU - Ito, Eisuke
AU  - Ito E
FAU - Seki, Hiroyuki
AU  - Seki H
FAU - Ushikawa, Kenji
AU  - Ushikawa K
FAU - Katahira, Hiroshi
AU  - Katahira H
FAU - Yoshimoto, Katsuhiko
AU  - Yoshimoto K
FAU - Ohno, Hideki
AU  - Ohno H
FAU - Nagamatsu, Shinya
AU  - Nagamatsu S
FAU - Ishida, Hitoshi
AU  - Ishida H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Metabolism
JT  - Metabolism: clinical and experimental
JID - 0375267
RN  - 0 (Glucose Transporter Type 4)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Insulin)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - G4PX8C4HKV (Gliclazide)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - 3T3-L1 Cells
MH  - Adipocytes/*drug effects
MH  - Animals
MH  - Gliclazide/*pharmacology
MH  - Glucose/metabolism
MH  - Glucose Transporter Type 4/genetics/*metabolism
MH  - Hydrogen Peroxide/pharmacology
MH  - Hypoglycemic Agents/pharmacology
MH  - Insulin/pharmacology
MH  - *Insulin Resistance
MH  - Mice
MH  - Oxidative Stress
MH  - Protein Transport
EDAT- 2006/05/23 09:00
MHDA- 2006/07/13 09:00
CRDT- 2006/05/23 09:00
PHST- 2005/06/23 00:00 [received]
PHST- 2006/01/08 00:00 [accepted]
PHST- 2006/05/23 09:00 [pubmed]
PHST- 2006/07/13 09:00 [medline]
PHST- 2006/05/23 09:00 [entrez]
AID - S0026-0495(06)00042-4 [pii]
AID - 10.1016/j.metabol.2006.01.019 [doi]
PST - ppublish
SO  - Metabolism. 2006 Jun;55(6):722-30. doi: 10.1016/j.metabol.2006.01.019.