Quin 2 and manganese define multiple alterations in cellular calcium homeostasis in diabetic rat pancreas.
The effects of streptozocin-induced diabetes on Ca2+ fluxes and intracellular free-Ca2+ [( Ca2+]i) levels were studied in isolated rat pancreatic acini. The basal rates of 45Ca influx in acini and of 45Ca efflux from acini that were preloaded with 45Ca were similar in normal and diabetic rats. The gastrointestinal hormone cholecystokinin octapeptide (CCK-8, 0.1 nM) and the Ca2+ ionophore A23187 (2 microM) increased 45Ca influx to the same extent in both groups of acini. CCK-8 and the divalent cation manganese exerted marked stimulatory effects on 45Ca efflux. In contrast to the rapid effect of CCK-8 on 45Ca efflux, the effect of manganese was slow in onset and was greater in diabetic rat acini. The diabetic state was also associated with a significant decrease in resting [Ca2+]i levels, as determined with the Ca2+ indicator quin 2. Furthermore, the ability of CCK-8 to raise [Ca2+]i levels was significantly attenuated in these cells. Insulin did not alter either basal or CCK-8-mediated increases in [Ca2+]i levels. Our findings suggest that insulin deficiency is associated with multiple alterations in Ca2+ homeostasis in the pancreatic acinar cell. These include a decrease in basal [Ca2+]i levels, perturbations in the signal transduction system that mediates the rapid mobilization of [Ca2+]i after CCK-8-receptor binding, and enhanced sensitivity to the actions of manganese on intracellular Ca2+ pools.
D000634:Aminoquinolines; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D003593:Cytoplasm / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005456:Fluorescent Dyes; D006706:Homeostasis; D007700:Kinetics; D008297:Male; D008345:Manganese / Q000494:pharmacology*; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012844:Sincalide / Q000494:pharmacology
D000634:Aminoquinolines; D002132:Calcium Radioisotopes; D005456:Fluorescent Dyes; D000001:Calcimycin; D008345:Manganese; D012844:Sincalide; C035739:Quin2; D002118:Calcium