Summary. The in vivo effects of vasoactive intestinal potypeptide (VIP), secretin and two different molecular forms of gastrin, gastrin 17 and pentagastrin, on basal and stimulated insulin secretion have been investigated in the mouse. All these peptides induced a moderate dose-dependent increase in basal insulin secretion. The different polypeptides showed complex effects on insulin release stimulated by glucose, the chotinergic agonist carbachol or the ,6-adrenergic agonist L-isop~opylnor.adrenaline (L-IPNA), these effects being dependent on the nature of the secretagogue. VIP and secretin both potenti 7 ated glucose-induced insulin release. Seeretin inhibited insulin secretion induced by caibachol and L-IPNA, whereas VIP potentiated L-IPNA-induced insulin secretion and had no influence on the effect of carbachol. Gastrin 17 and pentagastrin did not affect glucose-or carbachol-induced insulin release, whereas they inhibited L-IPNA-induced insulin secretion. The results suggest that VIP, secretin and gastrin display their effects on insulin secretion through different mechanisms. The results indirectly suggest the existence of separate insulin secretory pathways which operate differently, or at least partly differently, after glucose stimulation, cholinergie stimulation, and fl-adrenergic stimulation.Key words: VIP, secretin, gastrin, basal insulin secretion, stimulated insulin secretion, cholinergic stimulation, fl-adrenergic stimulation, glucose stimulation, in vivo, mouse.Several gastrointestinal endocrine polypeptides are known to affect insulin secretion [1,2]. Oral intake of glucose is followed by a greater insulin release than IV glucose administration, despite a lower blood glucose level. This potentiated response seems to be due to the release of gastro-intestinal peptides, the socalled incretin effect [3]. Peptides produced by intrapancreatic cells, endocrine and neural, may also regulate insulin secretion by a paracrine effect [4]. Some of these polypeptides show similarities in chemical structure and can therefore be grouped into two families [5], the glucagon family including glucagon, vasoactive intestinal polypeptide (VIP), secretin, and gastric inhibitory polypeptide (GIP), and the gastrin family including cfiolecystokinin (CCK) and gastrin.Recently it was demonstrated that some of the newly discovered gastrointestinal polypeptides interfere with the insulin secretory mechanisms in a complex manner, the effects on stimulated insulin secretion being highly dependent on the nature of the secretagogue [6]. The aim of the present investigation was to characterise further the effect of gastrointestinal polypeptides on basal and stimulated insulin release, and to compare effects of peptides belonging to the same polypeptide family with each other and with members of the other family. For this purpose we selected VIP and secretin on one hand and two different molecular forms of gastrin on the other. The in vivo insulin-releasing properties of these polypeptides were investigated under identical experim...