The effect of multiple injections of cholecystokinin 26-33 on a- and p-cells of islets of Langerhans normal and in experimental type 1 diabetes mellitus

Abstract

The impact of multiple peripheral (intraperitoneal) and central (intracerebroventricular) administrations of cholecystokinin 26-33 (CCK-8) octapeptide on the function of a- and /3- cells of the islets of Langerhans was studied in investigations made on normal rats and rats with experimental streptosotocine-induced type 1 diabetes mellitus. Insulin in /З-cells and glucagon in а-cells were found by indirect immunofluorescence. Both routes of administration to normal animals were shown to lead to the suppressed secretion of insulin with decreased food intake. At the same time the central administration of CCK-8, unlike the peripheral one, caused a sig­nificant (p < 0.05) rise in the level of glycemia and enhanced glucagon production in а-cells, while the administrations of the peptide to diabetic animals resulted a significant increase in the blood concentration of insulin (p < 0.05), to the lower level of glycemia (p < 0.05) and to suppressed polyphagia (p < 0.01), which is associated with the activation of /З-cell function and with the suppression of the pathologically high activity of а-cells. The established facts suggest that neuroendocrine interactions are impaired in diabetes mellitus and confirm the previously made suggestions that cholecystokinin plays an important role in the pathogenesis of this disease.