Gastrectomy induces impaired insulin and glucagon secretion: evidence for a gastro-insular axis in mice

1. Mice were subjected to gastrectomy (GX) or food deprivation (24 h). The release of insulin and glucagon in response to different secretagogues was monitored in vivo and in isolated islets 3-4 weeks after surgery. 2. GX animals responded to glucose with an impaired glucose tolerance and a poor increase in plasma insulin. Islets from GX or food-deprived mice disp layed impaired insulin release to high glucose and enhanced glucagon releas e at low glucose. 3. After GX the insulinogenic index, Delta insulin (mu U ml(-1))/Delta gluc ose (mg ml(-1)), was suppressed by 65% after oral glucose and by 59% after I.V. glucose. The integrated insulin response after oral glucose was reduce d by 90 % in GX mice. After I.V. glucose the reduction was 67 %. 4. Carbachol-induced insulin release in. vivo was reduced after food depriv ation and exaggerated after GX. Carbachol-stimulated glucagon secretion was suppressed after GX and after food deprivation. A similar pattern was foun d in vitro. 5. Cyclic AMP activation (by the phosphodiesterase inhibitor isobutylmethyl xanthine or the adenylate cyclase stimulator forskolin) induced a greater i nsulin response in EX or food-deprived mice than in sham-operated, fed mice . A similar pattern was found in vitro. The glucagon response was enhanced in, vitro but not in vivo. 6. Crude extracts of rat oxyntic mucosa enhanced basal as well as glucose-i nduced insulin release from isolated islets, whereas glucagon release was m arkedly inhibited. The effects were dose dependent, the inhibition of gluca gon release being achieved at lower concentrations than the potentiation of glucose-induced insulin release. The active principle was inactivated by i ncubation with trypsin or leucine aminopeptidase. 7. The data suggest that a circulating agent, probably a peptide, from gast ric oxyntic mucosa stimulates glucose-induced insulin secretion. It also su ppresses glucagon secretion. The GX evoked impairment of the insulin (and g lucagon) response to glucose is partly compensated for by an enhanced insul in response to cholinergic and/or cyclic AMP activation.