Summary
The in vivo effects of vasoactive intestinal polypeptide (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 cholinergic agonist carbachol or the β adrenergic agonist L-isopropylnoradrenaline (LIPNA), these effects being dependent on the nature of the secretagogue. VIP and secretin both potentiated glucose-induced insulin release. Secretin inhibited insulin secretion induced by carbachol and LIPNA, 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, cholinergic stimulation, and β-adrenergic stimulation.
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Rehfeld JF (1972) Gastrointestinal hormones and insulin secretion. Scand J Gastroenterol 7: 289–292
Brown JC, Otte SC (1978) Gastrointestinal hormones and the control of insulin secretion. Diabetes 27: 782–787
Creutzfeldt W (1979) The incretin concept today. Diabetologia 16: 75–85
Unger RH, Orci L (1977) Possible roles of the pancreatic D- cell in the normal and diabetic states. Diabetes 26: 241–244
Dockray GJ (1977) Molecular evolution of gut hormones: application of comparative studies on the regulation of digestion. Gastroenterology 72: 344–358
Lundquist I, Sundler F, Ahrén B, Alumets J, Håkanson R (1979) Somatostatin, pancreatic polypeptide, substance P, and neurotensin: Cellular distribution and effects on stimulated insulin secretion in the mouse. Endocrinology 104: 832–838
Rerup C, Lundquist I (1966) Blood glucose level in mice. I. Evaluation of a new technique of multiple serial sampling. Acta Endocrinol (Kbh) 52: 357–367
Heding L (1966) A simplified insulin radioimmunoassay method. In: Donato L, Milhaud G, Sirchis J (eds) Labelled proteins in tracer studies. Euratom, Brussels, p 345–350
Bruss ML, Black AL (1978) Enzymatic microdetermination of glycogen. Anal Biochem 84: 309–312
Larsson L-I, Fahrenkrug J, Schaffalitzky de Muckadell O, Sundler F, Håkanson R, Rehfeld JF (1976) Localization of vasoactive intestinal polypeptide (VIP) to central and peripheral neurons. Proc Natl Acad Sci USA 73: 3197–3200
Sundler F, Alumets J, Håkanson R, Fahrenkrug J, Schaffalitzky de Muckadell O (1978) Peptidergic (VIP) nerves in pancreas. Histochemistry 55: 173–176
Fahrenkrug J (1979) Vasoactive intestinal polypeptide: measurement, distribution and putative neurotransmitter function. Digestion 19: 149–169
Larsson L-I, Rehfeld JF (1979) Peptidergic and adrenergic innervation of pancreatic ganglia. Scand J Gastroenterol 14: 433–437
Larsson L-I, Sundler F, Alumets J, Håkanson R, Schaffalitzky de Muckadell OB, Fahrenkrug J (1977) Distribution, ontogeny and ultrastructure of the mammalian secretin cell. Cell Tissue Res 181: 361–368
Lindkear Jensen S, Fahrenkrug J, Holst JJ, Vagn Niesen O, Schaffalitzky de Muckadell OB (1978) Secretory effects of vasoactive intestinal polypeptide (VIP) on the isolated perfused porcine pancreas. Am J Physiol 235: E387-E391
Ohneda A, Ishii S, Horigome K, Chiba M, Sakai T, Kai Y, Watanabe K, Yamagata S (1977) Effect of intrapancreatic administration of vasoactive intestinal peptide upon the release of insulin and glucagon in dogs. Horm Metab Res 9: 447–452
Kaneto A, Kaneko T, Kajinuma H, Kosaka K (1977) Effect of vasoactive intestinal polypeptide infused intrapancreatically on glucagon and insulin secretion. Metabolism 26: 781–786
Makhlouf GM, Yau WM, Zfass AM, Said SI, Bodanszky M (1978) Comparative effects of synthetic and natural vasoactive intestinal peptide on pancreatic and biliary secretion and on glucose and insulin blood levels in the dog. Scand J Gastroenterol 13: 759–765
Schebalin M, Said SI, Makhlouf GM (1977) Stimulation of insulin and glucagon secretion by vasoactive intestinal peptide. Am J Physiol 232: E197-E200
Turner DS, Etheridge L, Marks V, Brown JC, Mutt V (1974) Effectiveness of the intestinal polypeptides IRP, GIP, VIP and motilin on insulin release in the rat. Diabetologia 10: 459–463
Unger RH, Ketterer H, Dupré J, Eisentraut AM (1967) The effects of secretin, pancreozymin, and gastrin on insulin and glucagon secretion in anesthetized dogs. J Clin Invest 46: 630–645
Lerner RL (1977) The augmentation effect of secretin on the insulin responses to known stimuli: specificity for glucose. J Clin Endocrinol Metab 45: 1–9
Enk B (1976) Secretin induced insulin response. Acta Endocrinol (Kbh) 82: 312–317
Fahrenkrug J, Schaffalitzky de Muckadell OB, Kühl C (1978) Effect of secretin on basal- and glucose-stimulated insulin secretion in man. Diabetologia 14: 229–234
Desbuquois B, Landat MM, Landat Ph (1973) Vasoactive intestinal polypeptide and glucagon: stimulation of adenylate cyclase activity via distinct receptors in lever and fat cell membranes. Biochem Biophys Res Commun 53: 1187–1194
Christophe JP, Conlon TP, Gardner JD (1976) Interaction of porcine vasoactive intestinal peptide with dispersed pancreatic aciner cells from guinea pig. Binding of radioiodinated peptide. J Biol Chem 251: 4629–4634
Rehfeld JF, Stadil F, Malmström J, Miyata M (1975) Gastrin heterogeneity in serum and tissue: a progress report. In: Thompson JC (ed) Gastrointestinal hormones. University of Texas Press, Austin London, p 43–58
McGuigan JE (1968) Gastric mucosal intracellular localization of gastrin by fluorescence. Gastroenterology 55: 315–327
Dubois PM, Paulin C, Chayvialle JA (1976) Identification of gastrin-secreting cells and cholecystokinin-secreting cells in the gastointestinal tract of the human fetus and adult man. Cell Tissue Res 175: 351–356
Larsson L-I, Rehfeld JF, Sundler F, Håkanson R (1976) Pancreatic gastrin in foetal and neonatal rats. Nature 262: 609–610
Uvnäs-Wallensten K, Rehfeld JF, Larsson L-I, Uvnäs B (1977) Heptadecapaptide gastrin in the vagal nerve. Proc Natl Acad Sci USA 74: 5707–5710
Rehfeld JF (1971) Effect of gastrin and its C-terminal tetrapeptide on insulin secretion in man. Acta Endocrinol (Kbh) 66: 169–176
Rehfeld JF, Stadil F (1973) The effect of gastrin on basal- and glucose-stimulated insulin secretion in man. J Clin Invest 52: 1415–1426
Kuzuya T, Kajinuma H, Sando H, Hayashi M, Ide T, Kosaka K (1978) Comparison of the early time courses of the release of insulin that follow injections of tetragastrin, tolbutamide, xylitol, and glucose into the pancreatic artery of dogs. Diabetes 27: 1189–1195
Grossman MI (1970) Gastrin, cholecystokinin and secretin act on one receptor. Lancet I: 1088–1089
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Ahrén, B., Lundquist, I. Effects of vasoactive intestinal polypeptide (VIP), secretin and gastrin on insulin secretion in the mouse. Diabetologia 20, 54–59 (1981). https://doi.org/10.1007/BF00253818
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DOI: https://doi.org/10.1007/BF00253818