Stimulation of insulin secretion and improvement of glucose tolerance in rat and dog by the P2y-purinoceptor agonist, adenosine-5'-O-(2-thiodiphosphate).
1. In vivo effect of a P2y-purinoceptor agonist, adenosine-5'-O-(2-thiodiphosphate) (ADP beta S), on insulin secretion and glycaemia were studied both in rats and dogs. 2. In anaesthetized rats, i.v. administered ADP beta S (0.2 mg kg-1) produced an insulin response dependent on the nutritional state of the animals, since we observed only a transient increase in overnight-fasted rats and a sustained insulin secretion followed by a reduction in plasma glucose levels in fed rats. During an i.v. glucose tolerance test, ADP beta S enhanced insulin release and thus increased the glucose disappearance rate. 3. In anaesthetized fasted dogs, i.v. administered ADP beta S (0.1 mg kg-1) increased pancreaticoduodenal insulin output and slightly decreased blood glucose levels. 4. In conscious fasted dogs, orally administered ADP beta S (0.1 mg kg-1) transiently increased insulinemia and punctually reduced glycaemia. Furthermore, during an oral glucose tolerance test, orally administered ADP beta S at the same dose markedly enhanced insulin secretion and consequently reduced the hyperglycaemia. 5. In conclusion, the P2y-agonist, ADP beta S, is a potent insulin secretagogue in vivo, improves glucose tolerance and is effective after oral administration. Thus, the P2y-purinoceptors of the beta cell may be a target for new antidiabetic drugs.
Faculté de Médecine, URA 599 du CNRS, Montpellier, France.
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Hillaire-Buys
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Bertrand
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Chapal
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Puech
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Ribes
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Loubatières-Mariani
D000244:Adenosine Diphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000758:Anesthesia; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004386:Duodenum / Q000098:blood supply; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D010179:Pancreas / Q000098:blood supply; D051381:Rats; D017208:Rats, Wistar; D011983:Receptors, Purinergic / Q000187:drug effects*; D012039:Regional Blood Flow / Q000187:drug effects; D013268:Stimulation, Chemical; D013873:Thionucleotides / Q000494:pharmacology*
D001786:Blood Glucose; D007328:Insulin; D011983:Receptors, Purinergic; D013873:Thionucleotides; C030812:adenosine 5'-O-(2-thiodiphosphate); D000244:Adenosine Diphosphate