MODULATION OF THE EFFECT OF HUMORAL-MEDIATED CYTOTOXICITY ON ISOLATEDRAT PANCREATIC-ISLETS BY GLUCOSE

Rat islets of Langerhans exposed for 20 h at high glucose (20 mmol/l) to 50% or 20% experimentally raised rabbit anti-rat islet cell surface antiserum (ICSA-positive serum) plus complement exhibited an irrevers ible loss of glucose-stimulated insulin secretion. In contrast, islets treated with 50% ICSA-positive serum at low glucose (5.5 mmol/l) coul d overcome this alteration within a subsequent 48 h recovery period at 10 mmol/1 glucose in the absence of ICSA, and islets affected at 5.5 mmol/l glucose by 200/o ICSA-positive serum even retained the insulin secretory potential and responded on glucose challenge already immedia tely after the removal of ICSA. The islet insulin content was reduced by the effect of 50% as well as of 20% ICSA-positive serum and complem ent irrespective of whether the glucose level amounted to 5.5 or 20 mm ol/l during serum influence. However, islets altered in a normoglycaem ic environment at 5.5 mmol/l glucose by 20% ICSA-positive serum restor ed their insulin content up to the level of control islets, whereas th ose islets affected under hyperglycaemic conditions at 20 mmol/l gluco se only partially recovered. Thus, beta-cell loss and/or impairment of the insulin secretory mechanisms result from the simultaneous action of humoral-mediated anti-islet cytotoxicity and elevated glucose level , and cause the diminished insulin secretory potential of the islets. These results support the hypothesis that decreasing the insulin secre tory activity of beta cells may protect them from cytotoxic immunologi cal attacks.