Studies of the cholinergic receptors involved in the secretion of insulin using isolated perfused rat pancreas

Abstract

Studies of ~he 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 ~M in the presence of a concentration of glucose of 1.5 g/l, 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 ~M of acetylcholine, the first phase of stimulation always appeared; during the second phase some par/creases 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 acetyleholine. The muscarinic nature of the cholinergie receptors implicated in the secretion of insulin was demonstrated by the use of: --Atropine which completely blocked the effects of acetylcholhm, --Musearine which produced the same effects as aeetylcholine on our pancreas preparation, effects which were equally inhibited by atropine. The cholinergie receptors of the endocrine beta cell of the islet of Langerhans of the pancreas are therefore of the muscarinic type.

Vagal, Cholinergic Regulation of Pancreatic Polypeptide Secretion

“…9) In acttial in-culature (27) and for stimulation of insulin release from the isolated perfused rat pancreas (28 From these three studies taken together it can be argued: that efferent, vagal stimuilation is a potent release mechanism for PP; that the vagal pathway includes a peripheral neurone activated by nicotinic receptors below the diaphragm; and that the final mediator probably mainly is acetylcholine acting on muscarinic receptors.…”

The pathogenesis of NIDDM: the role of the pancreatic beta cell

“…1). The sensitivity of the beta cell to this agonist combination, which had been observed over 20 years ago [13], suggested to us that any perturbation in terms of stimulant presentation (either glucose or cholinergic agonists) might be accompanied by significant changes in insulin output. This line of reasoning suggests a biochemical basis for the hyperinsulinaemia of obesity and prediabetes.…”

“…Second, and perhaps ironically, over the physiologic range of postprandial glucose levels, glucose by itself has only modest stimulatory effects on insulin secretion [9][10][11][12]. However, the insulin stimulatory effect of modest glycaemia is markedly augmented both in vivo and in vitro by the simultaneous presence of the neurotransmitter acetylcholine [13], the neurohumoral agonist cholecystokinin (CCK) [14], and other gut hormones such as glucagon-like peptide-1 (GLP-1) [15] and gastric inhibitory polypeptide (GIP) [14]. In the case of the former two stimulants, their ability to amplify secretion results from receptor-mediated increases in the hydrolysis of membrane PI [16,17].…”

A Link between Insulin Resistance and Hyperinsulinemia: Inhibitors of Phosphatidylinositol 3-Kinase Augment Glucose-Induced Insulin Secretion from Islets of Lean, But Not Obese, Rats1

“…Even in the presence of 6 mm (108 mg/100 ml) glucose and a level of cholinergic agonist similar to that used to study the effects of cholinergic stimulation in islets and other tissues (20,38), the inclusion of 50 nm wortmannin enhanced insulin secretion. When islets were stimulated with 8 mm glucose, 1 m carbachol, and 50 nm wortmannin, an increase in peak insulin release rates approaching that produced in response to 20 mm glucose alone were noted.…”