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.
Grapengiesser
E
E
Department of Medical Cell Biology, University of Uppsala, Sweden.
Gylfe
E
E
Hellman
B
B
D000496:Alloxan / Q000633:toxicity*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008820:Mice, Obese; D010507:Periodicity; D013311:Streptozocin / Q000633:toxicity*; D014044:Tolbutamide / Q000494:pharmacology
D013311:Streptozocin; D000496:Alloxan; D014044:Tolbutamide; D005947:Glucose; D002118:Calcium