title: Alloxan reversibly impairs glucagon release and glucose oxidation by pancreatic A2-cells.
abstract: Alloxan is known as a selective B-cell cytotoxic substance, and there is so far little evidence for a direct toxic effect on the other islet cell types. To elucidate further whether such effects occur, the actions of alloxan on glucagon release and glucose oxidation were studied in isolated normal or A(2)-cell-rich pancreatic islets of the guinea pig. The A(2)-cell-rich islets were obtained from animals injected with streptozotocin 1-2 weeks before islet isolation. After exposure to alloxan (2 or 5mm) in vitro for 30min at 4 degrees C, the islets were incubated in media containing either 1.7mm-glucose or 16.7mm-glucose plus 30m-i.u. of bovine insulin/ml. In both types of islet, alloxan abolished the ability of glucose and insulin both to decrease glucagon release and to increase the rate of glucose oxidation. A high concentration of glucose (28mm) during exposure to alloxan protected against these injurious effects. Tissue culture of alloxan-treated islets for 24h in 5.5mm-glucose restored neither the suppressive effect of glucose on glucagon release nor the inhibition of glucose oxidation of the A(2)-cells. However, culture for 1 week completely normalized both the glucagon-secretory response and glucose oxidation by both kinds of islets. It is therefore concluded that alloxan affects the secretory mechanism of not only the B-cell but also of the islet A(2)-cell, although this latter cell type is not primarily destroyed by the drug. The data furthermore support the concept of a relationship between glucose metabolism and the glucose-mediated glucagon release of the A(2)-cell.
mesh_terms: D000496:Alloxan / Q000494:pharmacology*; D000818:Animals; D046508:Culture Techniques; D005934:Glucagon / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006168:Guinea Pigs; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male
chemical_list: D000496:Alloxan; D005934:Glucagon; D005947:Glucose