ATP enhances exocytosis of insulin secretory granules in pancreatic islets under Ca2+-depleted condition.
Glucose and other nutrients have been shown to stimulate insulin release from pancreatic islets under Ca2+-depleted condition when protein kinase A (PKA) and protein kinase C (PKC) are activated simultaneously. We investigated the role of metabolic nucleotide signals including ATP, ADP, and GTP in exocytosis of insulin secretory granules under Ca2+-depleted condition using electrically permeabilized rat islets. ATP under PKC activation augmented insulin release concentration-dependently by 100 nM 12-O-tetradecanoyl-phorbol-13-acetate (TPA) in Ca2+-depleted condition, while ADP could not suppress ATP-dependent insulin release in this condition. Neither GTP nor activated PKA in the absence of PKC activation increased insulin release under Ca2+-depleted condition in the presence of ATP, but both enhanced insulin secretion in the presence of ATP when PKC was activated. In conclusion, activated PKC and the presence of ATP both are required in the insulin secretory process under Ca2+-depleted condition. While PKA activation and GTP cannot substitute for PKC activation and ATP, respectively, under Ca2+-depleted condition, they enhance ATP-dependent insulin secretion when PKC is activated.
Shimono
Dai
D
Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
Fujimoto
Shimpei
S
Mukai
Eri
E
Takehiro
Mihoko
M
Nabe
Koichiro
K
Radu
Razvan Gheorghe
RG
Shimodahira
Makiko
M
Kominato
Rieko
R
Aramaki
Yo
Y
Nishi
Yuichi
Y
Funakoshi
Shogo
S
Yamada
Yuichiro
Y
Seino
Yutaka
Y
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D000266:Adenylyl Imidodiphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology*; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007328:Insulin; D000266:Adenylyl Imidodiphosphate; C022571:adenosine 5'-O-(3-thiotriphosphate); D000255:Adenosine Triphosphate; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium