Disappearance of glucose-induced oscillations of cytoplasmic Ca2+ in pancreatic beta-cells exposed to streptozotocin or alloxan.

Dual wavelength microfluorometry and the indicator fura-2 were employed for measuring cytoplasmic Ca2+ (Ca2+i) in individual pancreatic beta-cells isolated from ob/ob-mice. In most beta-cells, a rise of external glucose from 3 to 20 mM resulted in large amplitude oscillations in Ca2+i, superimposed on a basal level of 60-90 nM. The diabetogenic agents streptozotocin and alloxan (1-4.4 mM) rapidly abolished the glucose-induced oscillations of Ca2+i. The presence of a high glucose concentration during the exposure to the drugs counteracted the action of alloxan but not that of streptozotocin. Perturbation of the cyclic variations of Ca2+i by streptozotocin did not interfere with a glucose-induced increase of the ion in mildly affected beta-cells. The most advanced lesions obtained with the exposure to the diabetogenic agents were manifested as uncontrolled and sustained increases of Ca2+i. Although disrupting the intracellular Ca2+ homeostasis by separate mechanisms, streptozotocin and alloxan may finally kill the beta-cells by activating a common suicidal process due to an excessive rise of Ca2+i.