Effects of isoprenaline and glucagon on insulin secretion from pancreatic islets

Abstract

The effects of isoprenaline and glucagon on insulin secretion from pancreatic islets were investigated. In the presence of high concentrations of isoprenaline (10-50 mumol/l), glucose-induced (20 mmol/l) insulin secretion from isolated perifused mouse islets was inhibited. This inhibition was apparently mediated by alpha 2-adrenoceptors, as it was antagonized by rauwolscine. At low concentrations isoprenaline (0.1 or 1 mumol/l) did not affect glucose-induced (2.5; 10 or 20 mmol/l) insulin secretion from perifused mouse or rat islets, even if alpha 2-adrenoceptors were blocked by rauwolscine. A stimulatory effect of isoprenaline on insulin secretion was also not observed in the perfused rat pancreas. However, when incubated mouse islets were exposed to glucose (10 mmol/l), insulin secretion was further enhanced by isoprenaline (0.5 mumol/l). To elucidate the underlying mechanism, the effects of glucagon on insulin secretion were investigated, because glucagon is released from the pancreatic A-cells during stimulation with isoprenaline and is accumulated in the islets and the surrounding medium during incubations of pancreatic islets. Indeed, glucagon stimulated insulin secretion from perifused mouse islets in the presence of high glucose (10 or 15 mmol/l) concentrations but not of low glucose (5 mmol/l) concentrations. Thus it is concluded that direct beta-adrenergic stimulation of pancreatic B-cells does not occur in mouse or rat pancreatic islets. Augmentation of glucose-induced insulin secretion by isoprenaline observed in incubation systems can be explained as a result of stimulation by glucagon, which is released from pancreatic A-cells by isoprenaline.

The characteristics of β-adrenergic binding sites on pancreatic islets of Langerhans

“…These agents have been shown in vivo to suppress glucose-induced insulin secretion suggest¬ ing that activation of a-andrenoceptors may be a major influence in the regulation of insulin secretion. A recent study has been unable to demonstrate this effect (Zielmann, Schutte, Lenzen & Panten, 1985), but the concentration of the ß agonist and ß antag¬ onist were tenfold less than those employed in the present experiments, implying that sub-stimulatory concentrations of the drugs may have been used. The data obtained in the present study implies that the binding sites were ß-adrenergic receptor sites which are linked to an effector system (insulin secretion).…”

Neutral endopeptidase 24.11 is important for the degradation of both endogenous and exogenous glucagon in anesthetized pigs

“…Insulin levels increased during the first glucagon infusion in response to the glucagon-stimulated increase in blood glucose. Glucagon itself can directly stimulate insulin secretion but is unlikely to have had a large effect in the present study because of the low (5 mmol/l) glucose concentrations (49). The modest rise in insulin concentrations during the second infusion after candoxatril likely reflects the smaller glucose response and, hence, the reduced stimulus to the ␤-cell.…”

Glicentin-related pancreatic polypeptide inhibits glucose-stimulated insulin secretion from the isolated pancreas of adult male rats

“…Both GLP-1 and glucagon are reported to act on the pancreatic b-cell to enhance glucose-stimulated insulin secretion (GSIS) (Metz et al 1983;Zielmann et al 1985;Holst et al 1987;Shima et al 1988;Goke et al 1989;Ishizuka et al 1991;Jia et al 1995;Vahl et al 2003). However, we know of only one study reporting the effects of GRPP on GSIS.…”