Aims: 

Xerostomia and polydipsia are widespread complications of diabetes mellitus which are associated with impaired functioning of salivary glands; however their cellular mechanisms are not determined yet. We studied the changes in free Ca²⁺ concentration in the lumen of endoplasmic reticulum ([Ca²⁺] ER) of submandibular acinar cells under diabetic conditions.

Methods: 

Diabetes was induced by a single i.p. injection of streptozotocin (60 mg/kg b.w.). Imaging of [Ca²⁺] ER was performed using mag-fura-2/ AM in beta-escin-permeabilized acinar cells. Concentration of free calcium in intracellular solution ([Ca²⁺]_i) was clamped at the 30 nM and 100 nM.

Results: 

We have found the increase of the InsP3-induced calcium release and passive calcium leak from the ER under diabetic conditions. It was shown: i) rise in the amplitude of InsP3-induced [Ca²⁺] ER decrease by 48 ± 8% (p < 0.05, n = 11) at the [Ca²⁺]_i = 100 nM; ii) increase of 3 mcM InsP3-induced [Ca²⁺]ER decrease by 58 ± 11% (p < 0.05, n = 19) at the [Ca²⁺]_i = 30 nM; iii) dramatic prolongation of the half-time of agonist-induced [Ca²⁺] ER transient by 107 ± 12% (p < 0.01, n = 13) under diabetic conditions. We have also found that puromycin (0.5 mM), that removes nascent polypeptides from the ER-ribosome translocon pores, caused significant increase of the passive Ca²⁺ leak from the ER under the diabetes (0.094 ± 0.022 in diabetes vs. 0.068 ± 0.013 in control). We suggest that diabetes is accompanied with rise in sensitive of InsP3-receptors and increase in passive calcium leak from the ER under diabetic conditions in submandibular acinar cells.

Supported by JDRF grant.