Augmentation of basal insulin release from rat islets by preexposure to a high concentration of glucose.
We have found that preexposure to an elevated concentration of glucose reversibly induces an enhancement of basal insulin release from rat pancreatic islets dependent on glucose metabolism. This basal insulin release augmented by priming was not suppressed by reduction of the intracellular ATP or Ca(2+) concentration, because even in the absence of ATP at low Ca(2+), the augmentation was not abolished from primed electrically permeabilized islets. Moreover, it was not inhibited by an alpha-adrenergic antagonist, clonidine. A threshold level of GTP is required to induce these effects, because together with adenine, mycophenolic acid, a cytosolic GTP synthesis inhibitor, completely abolished the enhancement of basal insulin release due to the glucose-induced priming without affecting the glucose-induced increment in ATP content and ATP-to-ADP ratio. In addition, a GDP analog significantly suppressed the enhanced insulin release due to priming from permeabilized islets in the absence of ATP at low Ca(2+), suggesting that the GTP-sensitive site may play a role in the augmentation of basal insulin release due to the glucose-induced priming effect.
Fujimoto
S
S
Department of Metabolism and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Kyoto 606 - 8507, Japan. fujimoto@metab.kuhp.kyoto-u.ac.jp
Tsuura
Y
Y
Ishida
H
H
Tsuji
K
K
Mukai
E
E
Kajikawa
M
M
Hamamoto
Y
Y
Takeda
T
T
Yamada
Y
Y
Seino
Y
Y
D000255:Adenosine Triphosphate / Q000378:metabolism; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D003000:Clonidine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D003981:Diazoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018274:Electroporation; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007424:Intracellular Fluid / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008356:Mannoheptulose / Q000494:pharmacology; D009173:Mycophenolic Acid / Q000494:pharmacology; D009840:Oligomycins / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D007328:Insulin; D009840:Oligomycins; D013873:Thionucleotides; D006153:Guanosine Diphosphate; D005576:Colforsin; D008356:Mannoheptulose; C023427:guanosine 5'-O-(2-thiodiphosphate); D000255:Adenosine Triphosphate; D009173:Mycophenolic Acid; D005947:Glucose; D003000:Clonidine; D013755:Tetradecanoylphorbol Acetate; D003981:Diazoxide; D011188:Potassium; D002118:Calcium