Prior exposure to high glucose augments depolarization-induced insulin release by mitigating the decline of ATP level in rat islets.
A brief exposure to elevated glucose augments the insulin secretory response of islets to subsequent stimulation. The site of this priming effect of glucose in the mechanism of the regulation of insulin secretion is not completely known, however. Insulin release triggered by a depolarizing concentration of K+ in the presence of basal glucose is markedly enhanced in primed rat islets. To clarify the role of priming on Ca(2+) and ATP efficacy in the exocytotic apparatus, islets were electrically permeabilized to vary the intracellular Ca(2+) and ATP concentrations according to the extracellular medium, and insulin release was evaluated. Ca(2+) and ATP efficacy in Ca(2+)- and ATP-dependent insulin secretion was not affected by priming, and alteration of the intracellular Ca(2+) concentration after depolarization cannot account for the phenomenon. There was no difference in ATP content before depolarization between nonprimed and primed islets. Moreover, the decline in ATP level after depolarization with basal glucose was observed in both primed and nonprimed islets. However, a reduced decline in ATP level in the early phase was observed in primed islets. In addition, oligomycin, a mitochondrial metabolism inhibitor, abolished the difference in ATP level between primed and nonprimed islets, suggesting that mitochondrial ATP production may be linked to the phenomenon.
Fujimoto
Shimpei
S
Department of Metabolism and Clinical Nutrition, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. fujimoto@metab.kuhp.kyoto-u.ac.jp
Mukai
Eri
E
Hamamoto
Yoshiyuki
Y
Takeda
Tomomi
T
Takehiro
Mihoko
M
Yamada
Yuichiro
Y
Seino
Yutaka
Y
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005947:Glucose / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008356:Mannoheptulose / Q000494:pharmacology; D009840:Oligomycins / Q000494:pharmacology; D009994:Osmolar Concentration; D010539:Permeability; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
D007328:Insulin; D009840:Oligomycins; D008356:Mannoheptulose; D000255:Adenosine Triphosphate; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium; D002118:Calcium