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In the present work, we have studied adenosine-induced vasodilation in streptozotocin-induced diabetic rats and compared it to that observed in normal age-matched or weight-matched animals. Experiments were performed on a vascular bed, the isolated perfused pancreas, and a large vessel, the thoracic aorta, provided from the same animal. Vasodilator activity was assessed, for isolated pancreas, as the increase in flow induced by the infusion of 2 µM adenosine for 30 min, or for noradrenaline-contracted aortae, as the relaxant response to adenosine (1 µM–1 mM). In both preparations the results obtained with selective adenosine receptors ligands (CPA, CGS 21680 and NECA) agreed with the presence of adenosine receptor of A2a subtype. In normal animals, adenosine vasodilator activity on both preparations diminished with advancing age in the rat, while diabetes was associated with a decreased or increased responsiveness to adenosine in pancreatic vascular bed or aorta, respectively. Further, the involvement of nitric oxide (NO), in relaxant responses, was evaluated by the use of the NO synthase inhibitor N ω-nitro- l-arginine methyl ester ( l-NAME). In all groups of animals, the flow rate of isolated pancreas dropped in the presence of 200 µM l-NAME, but was restored by adenosine to the level observed without l-NAME. l-NAME (10 µM) significantly reduced the dilator response to adenosine in aortic rings from diabetic animals, but not in those from normal rats. These results showed that adenosine vasorelaxant activity is significantly but differentially altered by diabetes according to the origin of the vascular preparation, and suggest that NO is involved in the vasorelaxant activity of adenosine in large vessels of diabetic animals. The potential pathophysiological role of adenosine in the vascular complications of diabetes remains to be determined. [ABSTRACT FROM AUTHOR]

Two series of experiments with the isolated perfused rat pancreas were performed in parallel. The conditions differed only with respect to temperature, which was 37.5 °C in one series and 28 °C in the other. The lowering of the temperature decreased insulin secretion induced by glucose as well as the insulin response to tolbutamide and acetylcholine. Unlike insulin, glucagon secretion was not significantly modified by hypothermia. Our results suggest that the mechanisms involved in glucagon and insulin secretion are different. [ABSTRACT FROM AUTHOR]

Studies of the role and nature of the cholinergic receptors acting on the secretion of isolated perfused rat pancreas have shown the following: The infusion of acetylcholine at a dose of 2.5 μM in the presence of a concentration of glucose of 1.5 g/1, provoked a first phase of immediate and important stimulation of the secretion of insulin; this initial peak of insulin secretion was followed by a second phase during which a new less intense stimulation occurred; the latter was followed by an inhibition appearing at a time that depended on the pancreas used. At a dose of 0.5 μM of acetylcholine, the first phase of stimulation always appeared; during the second phase some pancreases were inhibited, others remained stimulated. - The peak of insulin secretion obtained by stimulation with acetylcholine during the first phase was dose related. - Eserine intensified the effects of acetylcholine. - The presence of glucose was essential for the insulinsecretory action of acetylcholine. The muscarinic nature of the cholinergic receptors implicated in the secretion of insulin was demonstrated by the use of: - Atropine which completely blocked the effects of acetylcholine, - Muscarine which produced the same effects as acetylcholine on our pancreas preparation, effects which were equally inhibited by atropine. The cholinergic receptors of the endocrine beta cell of the islet of Langerhans of the pancreas are therefore of the muscarinic type. [ABSTRACT FROM AUTHOR]

The stimulating action of tolbutamide on insulin secretion presents two components; the first is independent of the presence of glucose in the medium which perfuses the beta cells; the second is, on the contrary, dependent upon glucose. D-mannoheptulose and diazoxide permit the dissociation of these two components; the antagonistic effect of the first exerts itself uniquely on that part of the stimulating action of tolbutamide which is gluco-dependent; on the contrary, the antagonistic effect of the second exerts itself on both phases of the stimulating action of the sulfonamide. [ABSTRACT FROM AUTHOR]

Copyright of Diabetologia is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Diabetologia is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Diabetologia is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Diabetologia is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)