Transport of 1,5-anhydro-D-glucitol into insulinoma cells by a glucose-sensitive transport system.
The uptake of 1,5-anhydro-D-glucitol (1,5-AG) occurs by passive mechanisms in cells or tissues that have passive glucose transporters. It is known that serum 1,5-AG concentrations are reduced in patients with diabetes mellitus. To elucidate the metabolism of this substance and its physiological role in pancreatic beta-cells, we assayed 1,5-AG transport in the insulinoma-derived cell lines, RINr and MIN6. Both cell lines showed an insulin-insensitive, concentration-dependent uptake of 1,5-AG with a saturation time of approximately 120 min, and most of the 1,5-AG in the cytoplasm was in the free form. A biphasic saturation curve was obtained using a wide range of 1,5-AG concentrations, suggesting that accumulation was mediated by a high affinity and a low affinity transporter. The high affinity transporter had a K(m) of 10.4 in RINr cells and 13.0 mM in MIN6 cells, and the low affinity transporter had a K(m)100 times, being much higher than the physiological concentrations of 1,5-AG. These results indicate that the 1,5-AG carrier system in insulinoma cells is distinct from that in either the somatic cells or renal tubular cells. These findings also suggest that a unique 1,5-AG transport system is present in pancreatic beta-cells.
Yamanouchi
T
T
Department of Internal Medicine, University of Teikyo, Kaga Itabashi-ku, Tokyo 173, Japan.
Ogata
N
N
Yoshimura
T
T
Inoue
T
T
Ogata
E
E
Kawasaki
T
T
Kashiwabara
A
A
Muraoka
H
H
D002250:Carbon Radioisotopes; D003847:Deoxyglucose / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007340:Insulinoma; D007700:Kinetics; D009004:Monosaccharide Transport Proteins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010190:Pancreatic Neoplasms; D013696:Temperature; D014316:Tritium; D014407:Tumor Cells, Cultured
D002250:Carbon Radioisotopes; D009004:Monosaccharide Transport Proteins; D014316:Tritium; C006584:1,5-anhydroglucitol; D003847:Deoxyglucose; D005947:Glucose