Potentiation of Insulin Secretion in Vitro by Serotonin Antagonists

Feldman, Jerome M.; Quickel, Kenneth E.

doi:10.2337/diab.21.7.779

Cited by 46 publications

(27 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Concerning insulin release, our findings confirm the inhibitory effect of serotonin described by Feldman et al in pieces of hamster, rabbit and mouse pancreas [8,9,10] and extend the observations of these authors to another B-cell stimulus; i.e., arginine. The reduction of arginine-stimulated insulin release observed in the presence of 5-hydroxytryptophan, is in good agreement with previous "in vitro" and "in vivo" data obtained in rabbits and mice [15,16,17].…”

Section: Discussionsupporting

confidence: 91%

See 1 more Smart Citation

Inhibition of glucagon release by serotonin in mouse pancreatic islets

1977

View full text Add to dashboard Cite

Summary. In this work we have investigated the effect of serotonin on glucagon release in mouse pancreatic islets isolated by the collagenase technique.Incubation of the islets with serotonin (4 • 10-3mol/1) was associated with an inhibition of glucagon output both in the basal medium (3.3 mmol/l glucose) and in the presence of arginine (10 mmol/1). The inhibitory effect of serotonin on basal glucagon release was also apparent at concentrations of 2 • 10 -3 mol/l, 10 -3 tool/1 and 5 • 10 -4 mol/1. Addition of 5-hydroxytryptophan (4 • 10 -3 tool/l) to the incubation medium was without effect on basal glucagon output while it significantly reduced arginine-induced glucagon release. In contrast, tryptophan (4 X 10 -3 mol/l) provoked glucagon secretion. As inferred from our previous human studies, the present data indicate that serotonin is able to inhibit glucagon secretion. These findings provide further support for the participation of a serotoninergic mechanism in the control of A-cell function.Key words: Mouse pancreatic islets, glucagon, insulin, serotonin, 5-hydroxytryptophan, tryptophan, creatinine sulphate.In man, treatment with serotonin antagonists (cyproheptadine and methysergide) as well as with an inhibitor of serotonin synthesis (para-chlorophenylalanine) induces a potentiation of glucagon secretion. Because of these findings, we have suggested that serotonin modulates A-cell function by acting as an inhibitor [1]. To investigate this hypothesis further, in this work we have examined the effects of serotonin and its immediate precursor (5-hydroxytryptophan) on glucagon release in a preparation of isolated mouse pancreatic islets. In addition, insulin output was measured. Materials and MethodsThe preparation of pancreatic islets employed has been described in detail elsewhere [2]. Briefly, fourweek old male mice, fasted for 14 h, were used as pancreas donors. The islets were isolated by the collagenase technique [3], as modified by . Batches of 10 islets were incubated for 60 to 120 minutes in 2 ml of Krebs-Henseleit solution [5] (gas phase 95:5, CO2:O2), containing 0.2 g/100 ml bovine albumin (Cohn fraction V), 2000U of kallikrein-trypsin inhibitor (Trasylol), and 3.3 mmol/1 glucose. Conventionally, this solution will be referred to as "basal medium" throughout the text. In some experiments, arginine hydrochloride (10 mmol/1) was used as the glucagon secretagogue. Serotonin creatinine sulphate, 5-hydroxy-L-tryptophan, L-tryptophan and creatinine sulphate were added as described in the figures and text. All incubations were performed in a water bath at 37 ~ set at 60 strokes per minute.Glucagon and insulin were measured by radioimmunoassay [6,7]. Results are expressed as means + SEM. N indicates the number of independent experiments. The term experiment refers to a set of incubations performed at the same time with islets prepared from a pool of eight pancreases. Within each experiment, all factors were tested simultaneously employing from 6 to 10 incubation vials. Differences betwen values were tested...

show abstract

Section: Discussionsupporting

confidence: 91%

“…However, they are well within the range described for inhibition of insulin release by the pancreas of several species [8,9,10].…”

Section: Discussionmentioning

confidence: 78%

Inhibition of glucagon release by serotonin in mouse pancreatic islets

1977

View full text Add to dashboard Cite

show abstract

“…However, Feldman et al [12] have reported results which are at variance with our data with respect to the effect of Haloperidol on insulin release. They did not find any effect on glucose stimulated insulin release at a Haloperidol concentration of 10 .4 mol/l.…”

Section: Discussionsupporting

confidence: 54%

Haloperidol, a dopaminergic antagonist: Somatostatin-like inhibition of glucagon and insulin release from the isolated, perfused canine pancreas

Hermansen¹

1978

Diabetologia

View full text Add to dashboard Cite

Summary. The effect of haloperidol, a dopaminergic antagonist, on insulin and glucagon secretion was investigated using the isolated, perfused canine pancreas. Haloperidol at 4 x 10 .7 to 10 .5 mol/1 caused a dose-dependent inhibition of glucagon release both at low (25 mg/100 ml) and high glucose concentrations (150 mg/100 ml). At the low glucose concentration insulin release was already maximally suppressed. At the high glucose concentration haloperidol (4 × 10 -7 to 10 .5 mol/1) also caused a dosedependent inhibition of insulin release. Haloperidol (10 -5 mol/1) inhibited dramatically pancreatic A and B cell responses to isoproterenol (2 ng/ml), acetylcholine (1 ~tmol/1) and arginine (5mmol/1). The inhibitory effect of haloperidol on both glucagon and insulin release could be eliminated by increasing perfusate calcium concentration from 1.3 to 8.8 mmol/1. These findings suggested that haloperidol blocks glucagon and insulin release in a somatostatin-like manner by affecting a fundamental step of the stimulus-secretion coupling, probably by interfering with calcium handling of the pancreatic A and B cells.Key words: Isolated, perfused canine pancreas, haloperidol, acetylcholine, isoproterenol, arginine, calcium, somatostatin-like inhibition, insulin secretion, glucagon secretion.Falck and Hellman [1,2] have demonstrated that in many species the endocrine pancreatic cells contain monoamines, particularly serotonin and dopamine [3,4]. The physiological significance of these monoamines stored within the islet cells is unknown.* Presented in part at the 13 th Annual Meeting of the European Association for the Study of Diabetes, Geneva, Switzerland, September 1977During investigations on monoaminergic mechanisms in pancreatic islets we employed the dopaminergic antagonist haloperidol, which is purported to be a specific dopamine receptor blocking agent in tissues such as brain [5], exocrine pancreas [6] and renal and mesenteric vessels [7]. Using the isolated, perfused canine pancreas it was noted that this dopaminergic antagonist inhibited release of both glucagon and insulin.The purpose of the present study was to investigate further the effect of haloperidol on insulin and glucagon secretion from the isolated, perfused canine pancreas in order to elucidate the mechanisms by which this substance produces its bihormonal inhibitory actions. Material and MethodsMongrel dogs, fasted overnight, weighing 18-25 kg were used as pancreas donors. The technique for isolation of the canine pancreas and the perfusion system have been described in detail by Iversen [8,9]. In brief, the preparation consisted of the pancreas and the proximal 10 cm of the attached duodenum. A nonrecirculating medium consisting of a Krebs Ringer bicarbonate buffer containing dextran 40 g/1 (MW 75,000), 2 g/1 bovine albumin, glutamate, fumarate and pyruvate, each at a concentration of 5 mmol/l was introduced through the splenic and the coeliac arteries, and the total portal effluent was collected every 1 min. Oxygenation of the Krebs-Ringer bicarbo...

show abstract

“…2 and Table 1 show, the simultaneous presence of 100 /tM propranolol (PPL), 100 ,uM phenoxybenzamine (PBZ) and 10 aM atropine did not significantly alter the pattern of insulin release produced by 100 ItM veratridine. At these concentrations, the above blocking agents completely inhibit the effects of relatively high P. DONATSCH AND OTHERS concentrations of the respective agonists on insulin release (Feldman, Quickel & Lebowitz, 1972;Malaisse et al 1967).…”

Section: Effects Of Veratridine On Insulin Releasementioning

confidence: 99%

The functional significance of sodium channels in pancreatic beta‐cell membranes

Donatsch¹,

Lowe²,

Richardson³

et al. 1977

The Journal of Physiology

115

View full text Add to dashboard Cite

SUMMARY1. The existence and functional significance of Na channels in pancreatic fl-cell membranes were investigated by studying the effects of the plant alkaloid veratridine on the temporal release of insulin from perfused isolated rat islets of Langerhans.2. 100 /SM veratridine evoked a sustained threefold increase in insulin release which was almost completely inhibited by 3 /LM tetrodotoxin (TTX). This action of TTX was rapidly reversible.3. The simultaneous presence of 100 /tM propranolol, 100 /LM phenoxybenzamine and 10/M atropine did not alter the magnitude of the response to 100 #UM veratridine, indicating that the action of veratridine on the fl-cells was direct and was not mediated via the release of neurotransmitters from nerve endings within the islets.4. 45Ca uptake by isolated islets in static incubation was increased almost threefold by 100 ItM veratridine. This increase was completely inhibited by the simultaneous presence of 3 /LM TTX.5. Replacement of Nao by choline caused a transient fourfold increase in insulin release which was associated with an increase in the uptake of 45Ca from the extracellular space of similar magnitude. Subsequent exposure of islets to 100 /tM veratridine still evoked some insulin release but this only achieved 32 % of that secreted by islets exposed to veratridine in medium of normal [Na]0. 6. The addition of 2-5 mm CoCl2 to the medium caused a 62 5 % inhibition of veratridine-mediated insulin release.7. In Ca-free medium supplemented with 1 mm EGTA, 100 fUM veratridine evoked insulin release of equal magnitude and of similar temporal relationship to that obtained in the presence of normal [Ca]0. [Ca]i by altering the equilibria of intracellular Casequestering mechanisms. The small but significant reduction of glucosemediated insulin release by TTX indicates that glucose has a rather weak action on the Na channel and a more pronounced effect on the voltagedependent (o2+-blockable Ca channel.

show abstract

Potentiation of Insulin Secretion in Vitro by Serotonin Antagonists

Cited by 46 publications

References 8 publications

Inhibition of glucagon release by serotonin in mouse pancreatic islets

Inhibition of glucagon release by serotonin in mouse pancreatic islets

Haloperidol, a dopaminergic antagonist: Somatostatin-like inhibition of glucagon and insulin release from the isolated, perfused canine pancreas

The functional significance of sodium channels in pancreatic beta‐cell membranes

Contact Info

Product

Resources

About