IN-VIVO AND IN-VITRO EFFECTS OF SOMATOSTATIN AND INSULIN ON GLUCAGON-RELEASE IN A HUMAN GLUCAGONOMA

Inhibition of pancreatic glucagon secretion has been reported to be me diated by glucose, insulin and somatostatin. As no human pancreatic ct -cell lines are available to study in vitro the relative importance of insulin and glucose in the control of pancreatic glucagon release, we investigated a patient presenting with a malignant glucagonoma who un derwent surgical resection of the tumour. Functional somatostatin rece ptors were present as octreotide administration decreased basal glucag on and insulin secretion by 52 and 74%, respectively, The removed tumo ur was immunohistochemically positive for glucagon, chromogranin A and pancreatic polypeptide but negative for insulin, gastrin and somatost atin. The glucagonoma cells were also isolated and cultured in vitro. incubation experiments revealed that change from high (10 mM) to low(1 mM) glucose concentration was unable to stimulate glucagon secretion, A dose-dependent inhibition of glucagon release by insulin was howeve r, observed at low glucose concentration, These findings demonstrate t hat insulin could inhibit glucagon secretion in vitro in the absence o f elevated glucose concentrations, These data suggest, as observed in vivo and in vitro in several animal studies, that glucopenia-induced g lucagon secretion in humans is not mediated by a direct effect of low glucose on alpha-cells but possibly by a reduction of insulin-mediated alpha-cell suppression and/or an indirect neuronal stimulation of glu cagon release.