ATP-sensitive K+ channel-independent glucose action in rat pancreatic beta-cell.
The nature of ATP-sensitive K+ (K+ATP) channel-independent, insulinotropic action of glucose was investigated using non-glucose-primed pancreatic islets. When the beta-cell was depolarized with K+, glucose dose dependently stimulated insulin release despite inhibition of the K+ATP channel closure by diazoxide. K+ depolarization could be replaced with BAY K 8644, a calcium channel agonist. Prior fasting of rats and lowering ambient temperature greatly suppressed glucose oxidation and utilization by the islet cells and abolished insulin release in response to high glucose alone. However, under these conditions, the K+ATP channel-independent, glucose-induced insulin release was clearly demonstrable. p-Nitrophenyl-alpha-D-glucopyranoside (sweet taste inhibitor) but not its beta-isomer, neomycin (phospholipase C inhibitor) and staurosporine (C kinase blocker) inhibited the K+ATP channel-independent, insulinotropic action of glucose. For the K+ATP channel-independent glucose-induced insulin release 1) elevation of cytosolic calcium is required, 2) minute glucose metabolism is enough, if glucose metabolism is necessary, and 3) direct recognition of glucose molecule, phospholipase C, and protein kinase C appear to be involved.
Aizawa
T
T
Department of Geriatrics, Endocrinology and Metabolism, Shinshu University School of Medicine, Nagano-ken, Japan.
Sato
Y
Y
Ishihara
F
F
Taguchi
N
N
Komatsu
M
M
Suzuki
N
N
Hashizume
K
K
Yamada
T
T
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D003981:Diazoxide / Q000494:pharmacology; D004594:Electrophysiology; D005215:Fasting; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D005960:Glucosides / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008297:Male; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013696:Temperature
D005960:Glucosides; D007328:Insulin; D015221:Potassium Channels; C019502:4-nitrophenyl alpha-glucoside; D000255:Adenosine Triphosphate; D005947:Glucose; D003981:Diazoxide; D011188:Potassium