Involvement of cellular calcium in exocrine pancreatic insufficiency during streptozotocin-induced diabetes mellitus.

This study investigates the effects of the islet hormones insulin (Ins), glucagon (Glu), and somatostatin (Som) with nerve stimulation (EFS) acetylcholine (ACh) and cholecytokinin-octapeptide (CCK-8) on amylase secretion and intracellular free calcium concentration Ca(2+) in the pancreas of age-matched control and diabetic rats. Either Ins, Glu or Som elicited small increases in amylase secretion from the pancreas of age-matched control animals compared to a much larger increase in amylase secretion with either EFS, ACh or CCK-8. Combining the islet hormones with either EFS, ACh or CCK-8 resulted in marked potentiation of amylase output. In the diabetic pancreas, the islet hormones had no effect on amylase secretion compared to diabetic control. Moreover, either EFS, ACh or CCK-8 evoked a much smaller increase in amylase output compared to age-matched control. In addition, the islet hormones failed to potentiate the secretory effects of either EFS, ACh or CCK-8. In fura-2 loaded acinar cells from age-matched control pancreas either Ins or Glu elicited a small increase in Ca(2+) whereas Som had no effect. Both ACh and CCK-8 evoked large increases in Ca(2+) compared to control. Combining either Ins, Glu or Som with either ACh or CCK-8 resulted in a marked elevation in Ca(2+) compared to the responses obtained with either the islet hormones, ACh or CCK-8 alone. In diabetic fura-2 loaded pancreatic acinar cells, the islet hormones had no effect on Ca(2+) compared to control and moreover, the responses were much smaller than those obtained in acinar cells from age-matched control. Both ACh and CCK-8 induced large increases in Ca(2+) in diabetic acinar cells. However, combining the islet hormones with either ACh or CCK-8 failed to enhance Ca(2+) compared to the reponses obtained in acinar cells from age-matched control. The results suggests that Ca(2+) homeostasis is deranged during diabetes mellitus and this in turn is probably associated with reduced pancreatic amylase secretion.