Abstract
A number of studies have demonstrated that insulin resistance in the skeletal muscle plays a pivotal role in the insulin resistance associated with obesity and type 2 diabetes. A decrease in GLUT4 translocation from the intracellular pool to the plasma membranes in skeletal muscles has been implicated as a possible cause of insulin resistance. Herein, we examined the effects of an insulin-sensitizing drug, troglitazone (TGZ), on glucose uptake and the translocation of GLUT4 in L6 myotubes. The prolonged exposure (24 h) of L6 myotubes to TGZ (10-5 mol/l) caused a substantial increase in the 2-deoxy-[3H]D-glucose (2-DG) uptake without changing the total amount of the glucose transporters GLUT4, GLUT1, and GLUT3. The TGZ-induced 2-DG uptake was completely abolished by cytochalasin-B (10 μmol/l). The ability of TGZ to translocate GLUT4 from light microsomes to the crude plasma membranes was greater than that of insulin. Both cycloheximide treatment (3.5 × 10-6 mol/l) and the removal of TGZ by washing reversed the 2-DG uptake to the basal level. Moreover, insulin did not enhance the TGZ-induced 2-DG uptake additively. The TGZ-induced 2-DG uptake was only partially reversed by wortmannin to 80%, and TGZ did not change the expression and the phosphorylation of protein kinase B; the expression of protein kinase C (PKC)-λ, PKC-β2, and PKC-ξ; or 5′ AMP-activated protein kinase activity. α-Tocopherol, which has a molecular structure similar to that of TGZ, did not increase 2-DG uptake. We conclude that the glucose transport in L6 myotubes exposed to TGZ for 24 h is the result of an increased translocation of GLUT4. The present results imply that the effects of troglitazone on GLUT4 translocation may include a new mechanism for improving glucose transport in skeletal muscle.
| Original language | English |
|---|---|
| Pages (from-to) | 1093-1101 |
| Number of pages | 9 |
| Journal | Diabetes |
| Volume | 50 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Jan 1 2001 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Internal Medicine
- Endocrinology, Diabetes and Metabolism
Cite this
Troglitazone induces GLUT4 translocation in L6 myotubes. / Yonemitsu, Shin; Nishimura, Haruo; Shintani, Mitsuyo; Inoue, Ryou; Yamamoto, Yuji; Masuzaki, Hiroaki; Ogawa, Yoshihiro; Hosoda, Kiminori; Inoue, Gen; Hayashi, Tatsuya; Nakao, Kazuwa.
In: Diabetes, Vol. 50, No. 5, 01.01.2001, p. 1093-1101.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Troglitazone induces GLUT4 translocation in L6 myotubes
AU - Yonemitsu, Shin
AU - Nishimura, Haruo
AU - Shintani, Mitsuyo
AU - Inoue, Ryou
AU - Yamamoto, Yuji
AU - Masuzaki, Hiroaki
AU - Ogawa, Yoshihiro
AU - Hosoda, Kiminori
AU - Inoue, Gen
AU - Hayashi, Tatsuya
AU - Nakao, Kazuwa
PY - 2001/1/1
Y1 - 2001/1/1
N2 - A number of studies have demonstrated that insulin resistance in the skeletal muscle plays a pivotal role in the insulin resistance associated with obesity and type 2 diabetes. A decrease in GLUT4 translocation from the intracellular pool to the plasma membranes in skeletal muscles has been implicated as a possible cause of insulin resistance. Herein, we examined the effects of an insulin-sensitizing drug, troglitazone (TGZ), on glucose uptake and the translocation of GLUT4 in L6 myotubes. The prolonged exposure (24 h) of L6 myotubes to TGZ (10-5 mol/l) caused a substantial increase in the 2-deoxy-[3H]D-glucose (2-DG) uptake without changing the total amount of the glucose transporters GLUT4, GLUT1, and GLUT3. The TGZ-induced 2-DG uptake was completely abolished by cytochalasin-B (10 μmol/l). The ability of TGZ to translocate GLUT4 from light microsomes to the crude plasma membranes was greater than that of insulin. Both cycloheximide treatment (3.5 × 10-6 mol/l) and the removal of TGZ by washing reversed the 2-DG uptake to the basal level. Moreover, insulin did not enhance the TGZ-induced 2-DG uptake additively. The TGZ-induced 2-DG uptake was only partially reversed by wortmannin to 80%, and TGZ did not change the expression and the phosphorylation of protein kinase B; the expression of protein kinase C (PKC)-λ, PKC-β2, and PKC-ξ; or 5′ AMP-activated protein kinase activity. α-Tocopherol, which has a molecular structure similar to that of TGZ, did not increase 2-DG uptake. We conclude that the glucose transport in L6 myotubes exposed to TGZ for 24 h is the result of an increased translocation of GLUT4. The present results imply that the effects of troglitazone on GLUT4 translocation may include a new mechanism for improving glucose transport in skeletal muscle.
AB - A number of studies have demonstrated that insulin resistance in the skeletal muscle plays a pivotal role in the insulin resistance associated with obesity and type 2 diabetes. A decrease in GLUT4 translocation from the intracellular pool to the plasma membranes in skeletal muscles has been implicated as a possible cause of insulin resistance. Herein, we examined the effects of an insulin-sensitizing drug, troglitazone (TGZ), on glucose uptake and the translocation of GLUT4 in L6 myotubes. The prolonged exposure (24 h) of L6 myotubes to TGZ (10-5 mol/l) caused a substantial increase in the 2-deoxy-[3H]D-glucose (2-DG) uptake without changing the total amount of the glucose transporters GLUT4, GLUT1, and GLUT3. The TGZ-induced 2-DG uptake was completely abolished by cytochalasin-B (10 μmol/l). The ability of TGZ to translocate GLUT4 from light microsomes to the crude plasma membranes was greater than that of insulin. Both cycloheximide treatment (3.5 × 10-6 mol/l) and the removal of TGZ by washing reversed the 2-DG uptake to the basal level. Moreover, insulin did not enhance the TGZ-induced 2-DG uptake additively. The TGZ-induced 2-DG uptake was only partially reversed by wortmannin to 80%, and TGZ did not change the expression and the phosphorylation of protein kinase B; the expression of protein kinase C (PKC)-λ, PKC-β2, and PKC-ξ; or 5′ AMP-activated protein kinase activity. α-Tocopherol, which has a molecular structure similar to that of TGZ, did not increase 2-DG uptake. We conclude that the glucose transport in L6 myotubes exposed to TGZ for 24 h is the result of an increased translocation of GLUT4. The present results imply that the effects of troglitazone on GLUT4 translocation may include a new mechanism for improving glucose transport in skeletal muscle.
UR - http://www.scopus.com/inward/record.url?scp=0035029808&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035029808&partnerID=8YFLogxK
U2 - 10.2337/diabetes.50.5.1093
DO - 10.2337/diabetes.50.5.1093
M3 - Article
C2 - 11334413
AN - SCOPUS:0035029808
VL - 50
SP - 1093
EP - 1101
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 5
ER -