インスリン分泌に関する研究 : 特にadenosineの影響について
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概要
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The effect of adenosine and its analogues on insulin release and content of ATP and cAMP of rat islets was investigated. Islets were isolated from Wistar male adult rats by collagenase method. Each 5 islets were incubated in Krebs-Henseleit bicarbonate buffer (KHBB) containing various agents for 60 minutes under a gas phase of 95% O_2-5% CO_2 after 20 minutes' preincubation in KHBB containing 3.3 mM glucose and 0.5% BSA. Insulin released in the medium was radioimmunoassayed with rat insulin as standard. Islets after the incubation were subjected to the determination of ATP and cAMP using enzymatic cycling method and radioimmunoassay, respectively. 1. 1 and 10 mM adenosine and 10 mM N^6-dihydroxyethyladenosine enhanced 8.3 mM glucoseinduced insulin release, but 1 and 10 mM adenine and 2.5, 5 and 10 mM 2'-deoxyadenosine did not. 2. 10 mM adenosine increased ATP and cAMP content in islets. 10 mM 2'-deoxyadenosine increased ATP content, but not cAMP content. 10 mM N^6-dihydroxyethyladenosine did not affect A TP content. 3. Insulin release induced by 10 mM adenosine was inhibited by 5 and 10 mM 2'-deoxyadenosine, but the increase of ATP content by adenosine was not altered by the same concentration of 2'-deoxyadenosine. 4. 100μM dipyridamol, inhibitor of intracellular uptake of adenosine, did not affect the effect of adenosine on insulin release from islets. The present observations showed that the increase of insulin release by adenosine was not associated with the elevation of ATP in islets, but seemed to be parallel with the change of cAMP content in islets, and that the penetrance of adenosine into B cells appeared not to be required in its potentiation of insulin release. Therefore, it was suggested that adenosine enhanced insulin release probably through the direct action on pancreatic B cell membrane and the consequent elevation of cAMP.
- 神戸大学の論文