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+)](i) 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+)](i) whereas Som had no effect. Both ACh and CCK-8 evoked large increases in [Ca(2+)](i) compared to control. Combining either Ins, Glu or Som with either ACh or CCK-8 resulted in a marked elevation in [Ca(2+)](i) 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+)](i) 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+)]( i) in diabetic acinar cells. However, combining the islet hormones with either ACh or CCK-8 failed to enhance [Ca(2+)](i) compared to the reponses obtained in acinar cells from age-matched control. The results suggests that [Ca(2+)](i) homeostasis is deranged during diabetes mellitus and this in turn is probably associated with reduced pancreatic amylase secretion.
Singh
J
J
Department of Biological Sciences, University of Central Lancashire, Preston, UK.
Yago
M D
MD
Adeghate
E
E
D000681:Amylases / Q000032:analysis / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000378:metabolism; D004558:Electric Stimulation; D010188:Exocrine Pancreatic Insufficiency / Q000209:etiology* / Q000378:metabolism; D005260:Female; D005456:Fluorescent Dyes; D016257:Fura-2; D005934:Glucagon / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007515:Islets of Langerhans / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012844:Sincalide / Q000494:pharmacology; D013004:Somatostatin / Q000494:pharmacology
D005456:Fluorescent Dyes; D007328:Insulin; D013004:Somatostatin; D005934:Glucagon; D000681:Amylases; D012844:Sincalide; D002118:Calcium; D016257:Fura-2