[Purinergic receptors and insulin secretion].
The stimulating effect of ATP on insulin secretion has been demonstrated by several authors both in vitro and in vivo. The kinetic study carried out on the isolated perfused pancreas of the rat, in the presence of a glucose concentration of 1.5 g/l, showed that the response was biphasic and dose-dependent for ATP concentrations ranging from 10(-6) to 10(-4) M. It can be seen from the results obtained with the natural nucleotides (ATP, ADP, AMP, adenosine, GTP, ITP, UTP, CTP), that there is a structure activity relationship. Some structural features are essential to elicit an insulin secretory effect: a purine base and 2 or 3 phosphate groups. The study with the structural analogues of ATP and ADP modified on the polyphosphate chain, shows the importance of the steric and electronic characteristics of the polyphosphate chain for induction of insulin secretion. The insulin-stimulating action of ATP seems to be selectively antagonized by 2, 2' pyridylisatogen. It is blocked neither by a cholinergic blocker (atropine), nor by a beta-adrenergic blocker (propranolol), nor by an adenosine antagonist (theophylline). In the present state of the experimental work, the results favour a purinergic receptor site to ATP or ADP on the beta-insulin-secretory cells. At least three factors are in favour of a type P2 receptor, according to the classification of purinergic receptors (Burnstock, 1978) : the order of relative potencies of the agonists: ATP greater than or equal to ADP much greater than AMP greater than or equal to adenosine, the lack of antagonist effect of theophylline and the selective antagonism of PIT.
D000244:Adenosine Diphosphate / Q000031:analogs & derivatives; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007700:Kinetics; D011122:Polyphosphates / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000502:physiology*; D011983:Receptors, Purinergic; D013268:Stimulation, Chemical; D013329:Structure-Activity Relationship
D007328:Insulin; D011122:Polyphosphates; D011956:Receptors, Cell Surface; D011983:Receptors, Purinergic; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D005947:Glucose
Récepteurs purinergiques et insulino-sécrétion.