Insulinotropic action of glutamate is dependent on the inhibition of ATP-sensitive potassium channel activities in MIN 6 beta cells.
To investigate the cellular mechanism of insulinotropic effect of glutamate in pancreatic beta cells, we utilized patch-clamp technique to monitor directly the activities of ATP-sensitive potassium channels (K(ATP) channels). Dimethylglutamate (5mM), a membrane-permeable analog of glutamate, augmented the insulin release induced by the stimulatory concentrations of glucose (p<0.05-0.01). In the cell-attached configurations, dimethylglutamate reversibly and significantly suppressed the K(ATP) channel activities (p<0.01). On the other hand, no significant effect was observed when glutamate itself was applied to the inside-out patches, whereas the prompt and reversible suppression was recorded in the case of ATP (p<0.01). These results indicate that the insulinotropic action of glutamate in beta cells could be derived from the inhibition of K(ATP) channel activities, probably due to generation of messengers via intracellular metabolism such as ATP.
Katsuta
Hidenori
H
Third Department of Internal Medicine, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan.
Ozawa
Sachihiko
S
Ninomiya
Tomonori
T
Shimoyama
Tatsuhiro
T
Ito
Eisuke
E
Tanaka
Toshiaki
T
Yamaguchi
Shinya
S
Katahira
Hiroshi
H
Nagamatsu
Shinya
S
Horie
Minoru
M
Ishida
Hitoshi
H
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000737:chemistry; D018698:Glutamic Acid / Q000737:chemistry* / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D051379:Mice; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar
D007328:Insulin; D015221:Potassium Channels; D018698:Glutamic Acid; D000255:Adenosine Triphosphate; D005947:Glucose; D011188:Potassium