In vivo and in vitro effects of adenosine-5'-O-(2-thiodiphosphate) on pancreatic hormones in dogs.
Adenosine-5'-O-(2-thiodiphosphate) (ADP beta S), a P2y purinergic agonist, has been shown to be a potent insulin secretagogue on the isolated rat pancreas. In the present work the effects of ADP beta S on insulin somatostatin, and glucagon secretions were investigated in dogs. In vivo, in anesthetized fasted dogs, i.v. ADP beta S (0.1 mg kg-1) induced an immediate increase in insulin and somatostatin-like immunoreactivity (SLI) but not in glucagon pancreaticoduodenal outputs. In conscious fasted dogs, i.v. ADP beta S (0.1 mg kg-1) produced an immediate and transient augmentation in plasma insulin levels but not in plasma SLI and glucagon levels. In vitro, the effects of ADP beta S were investigated on the isolated uncinate process of dog pancreas, from normal and alloxan-diabetic animals. In normal uncinate process, in presence of 8.3 mM glucose, ADP beta S (1 microM) stimulated insulin and SLI releases but not glucagon release. On uncinate process from diabetic animals, ADP beta S (1 microM) retained its stimulating effects but the responses were impaired as compared with normal dogs: Insulin response was drastically diminished and SLI response strongly enhanced. In conclusion, ADP beta S is a potent insulin secretory agent in dog. This P2y purinoceptor agonist, which exerts a direct stimulatory effect on pancreatic SLI, is interestingly devoid of direct glucagonotropic properties.
Hillaire-Buys
D
D
Faculté de Médecine, Laboratoire de Pharmacologie et Pharmacodynamie, Hôpital Lapeyronie, Montpellier, France.
Gross
R
R
Parés-Herbuté
N
N
Ribes
G
G
Loubatières-Mariani
M M
MM
D000244:Adenosine Diphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D004285:Dogs; D005934:Glucagon / Q000378:metabolism*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D013004:Somatostatin / Q000378:metabolism*; D013873:Thionucleotides / Q000494:pharmacology*
D007328:Insulin; D013873:Thionucleotides; C030812:adenosine 5'-O-(2-thiodiphosphate); D013004:Somatostatin; D000244:Adenosine Diphosphate; D005934:Glucagon