Grapengiesser E, Gylfe E, Hellman B
Department of Medical Cell Biology, University of Uppsala, Sweden.
Toxicology. 1990 Sep;63(3):263-71. doi: 10.1016/0300-483x(90)90189-n.
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.
采用双波长显微荧光测定法和荧光指示剂fura-2来测量从ob/ob小鼠分离出的单个胰腺β细胞中的细胞质Ca2+（Ca2+i）。在大多数β细胞中，细胞外葡萄糖浓度从3 mM升高到20 mM会导致Ca2+i出现大幅度振荡，叠加在60 - 90 nM的基础水平上。致糖尿病药物链脲佐菌素和四氧嘧啶（1 - 4.4 mM）能迅速消除葡萄糖诱导的Ca2+i振荡。在接触药物期间存在高葡萄糖浓度可抵消四氧嘧啶的作用，但不能抵消链脲佐菌素的作用。链脲佐菌素对Ca2+i周期性变化的干扰并不影响轻度受影响的β细胞中葡萄糖诱导的离子增加。接触致糖尿病药物后出现的最严重损伤表现为Ca2+i不受控制地持续增加。尽管链脲佐菌素和四氧嘧啶通过不同机制破坏细胞内Ca2+稳态，但由于Ca2+i过度升高，它们最终可能通过激活共同的自杀过程杀死β细胞。
