Glutamate is not a major conveyer of ATP-sensitive K+ channel-independent glucose action in pancreatic islet beta cell.
Insulinotropic action of glucose can be categorized as 1) triggering of release, 2) augmentation of exocytosis elicited by Ca2+, and 3) time-dependent potentiation (TDP) of the exocytotic machinery. Glucose-induced closure of ATP-sensitive K+ (K+ATP) channel is required for the first but not for the latter two. We examined the legitimacy of a novel hypothesis that glutamate is a conveyer of the K+ATP channel-independent glucose action, using intact rat pancreatic islets. To this end, we compared glucose and cell permeable glutamate donors such as dimethylglutamate and glutamine for their potency of augmentation and TDP in the presence of diazoxide (250 micromol/l), a K+ATP channel opener. One millimolar leucine was employed as an activator of glutamate dehydrogenase (GDH) as needed. A high concentration (16.7 mmol/l) of glucose applied simultaneously with a depolarizing concentration (50 mmol/l) of K+ augmented (5.80 fold) insulin release elicited by the latter. Pretreatment of the islets with 16.7 mmol/l glucose caused TDP so that insulin release subsequently elicited by 50 mmol/l K+ alone was enhanced (4.70 fold). The augmentation and TDP caused by dimethylglutamate and glutamine (10 mmol/l each), respectively, were very weak (12% of the glucose effect utmost), and dramatically enhanced upon activation of GDH by leucine. Insulinotropic effect of the glutamate donors, but not that of 50 mmol/l K+, was eliminated by 2 mmol/l NaN3, a mitochondrial poison. Glutamate per se serves as a weakly metabolizable mitochondrial fuel, but not a direct conveyer of the K+ATP channel-independent glucose action in the islet beta cell.
Yamada
S
S
Department of Aging Medicine and Geriatrics, Shinshu University School of Medicine, Matsumoto, Japan.
Komatsu
M
M
Sato
Y
Y
Yamauchi
K
K
Aizawa
T
T
Hashizume
K
K
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D018698:Glutamic Acid / Q000494:pharmacology / Q000502:physiology*; D005973:Glutamine / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D007328:Insulin; D015221:Potassium Channels; D005973:Glutamine; D018698:Glutamic Acid; D000255:Adenosine Triphosphate; D005947:Glucose; D011188:Potassium; D002118:Calcium