title: P2y purinoceptor responses of beta cells and vascular bed are preserved in diabetic rat pancreas.
abstract: 1. To investigate the effect of experimental diabetes on the P2y purinoceptor responses of pancreatic beta-cells and vascular bed, we used adenosine-5'-O-(2-thiodiphosphate) (ADP beta S), a potent and stable P2y agonist. This work was performed in the isolated perfused pancreas of the rat. 2. Diabetes was induced by streptozotocin (66 mg kg-1, i.p.). Five weeks after the induction of diabetes, on the day of pancreas isolation, the animals displayed marked hyperglycaemia (37.6 +/- 2.7 mM). Age-matched rats were used as controls. 3. Insulin response to a glucose stimulation from 5 to 10 mM was completely lost and stimulation of insulin release by the sulphonylurea, tolbutamide (185 microM), was drastically impaired in the diabetic pancreas (maximum responses were 1.5 +/- 0.4 and 7.0 +/- 1.4 ng min-1 for diabetic and age-matched rats respectively). 4. In contrast, in the diabetic pancreas ADP beta S (15 microM), infused in the presence of glucose 5 mM, elicited an immediate and significant insulin release similar to that observed in the age-matched pancreas (maximum responses were 7.6 +/- 1.5 and 6.7 +/- 1.3 ng min-1 respectively). This ADP beta S stimulating effect occurred independently of the glucose concentration (5, 8.3 and 28 mM) in the diabetic pancreas. On pancreatic vascular resistance, ADP beta S induced a similar vasodilatation in diabetic and age-matched rats. 5. In conclusion, ADP beta S retains its insulin stimulatory and vasodilator effects in experimental diabetes; P2y purinoceptors could therefore be considered as a new target for the development of antidiabetic drugs.
authors.affiliation: Faculté de Médecine, Laboratoire de Pharmacologie, CNRS, URA 599, Montpellier, France.
authors.forename: D
authors.initials: D
authors.lastname: Hillaire-Buys
authors.forename: R
authors.initials: R
authors.lastname: Gross
authors.forename: J
authors.initials: J
authors.lastname: Chapal
authors.forename: G
authors.initials: G
authors.lastname: Ribes
authors.forename: M M
authors.initials: MM
authors.lastname: Loubatières-Mariani
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D005934:Glucagon / Q000032:analysis; D006029:Glycosuria; D066298:In Vitro Techniques; D007328:Insulin / Q000032:analysis; D007515:Islets of Langerhans / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D010179:Pancreas / Q000098:blood supply*; D051381:Rats; D011919:Rats, Inbred Strains; D011983:Receptors, Purinergic / Q000502:physiology*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D011983:Receptors, Purinergic; D005934:Glucagon