EFFECTS OF ISLET HORMONES ON NERVE-MEDIATED AND ACETYLCHOLINE-EVOKED SECRETORY RESPONSES IN THE ISOLATED PANCREAS OF NORMAL AND DIABETIC RATS

This study employs the pancreas of normal and diabetic rats to investi gate the relationship between the endocrine and exocrine pancreas in t he control of exocrine secretion employing enzyme and immunohistochemi cal and physiological techniques. Acetylcholine esterase (ACh-E) posit ive nerves were distributed in the interacinar regions of the pancreas lying close to the exocrine cells. There was no difference between th e cholinergic innervation of the pancreas in normal and diabetic rat. Insulin (INS) immunopositive cells were observed in the peripheral and central portions of the Islet of Langerhans in the pancreas of normal rat. In the diabetic animals the number of INS-positive cells were de creased. In contrast, glucagon (GLU) and somatostatin (SOM)-immunoposi tive cells were identified mainly in the peripheral parts of the Islet s of Langerhans and their numbers increased markedly in the diabetic p ancreas. Insulin alone had no significant effect on amylase secretion in the normal pancreas whereas GLU and SOM evoked small increases in a mylase out compared to basal. In contrast, the islet hormones have no detectable secretory effect on the diabetic pancreas compared to contr ol. Both electrical field stimulation (EFS) of intrinsic secretomotor nerves and exogenous application of acetylcholine (ACh) resulted in ma rked increases in amylase secretion. In pancreatic acini and acinar ce lls ACh evoked dose-dependent increases in amylase release. In normal pancreatic segments a combination af either INS or GLU with EFS or ACh resulted in marked potentiation of amylase output. In contrast, SOM i nhibited the EFS-evoked amylase output but enhanced the secretory resp onse to ACh. In pancreatic acini and acinar cells from normal rat and in pancreatic segments from diabetic rats, the islet hormones had no p otentiating effect on the ACh-evoked secretory response. Similarly, in the diabetic rat the islet hormone had no effect on EFS-evoked amylas e output. In fura-2 loaded pancreatic acinar cells ACh-induced a marke d increase in intracellular free calcium concentration [Ca2+](i) compa red to basal. Either INS or GLU, but not SOM, elicited a small increas e in [Ca2+](i). Combining either INS or GLU with ACh resulted in a pot entiation of [Ca2+](i) compared with ACh alone. In contrast, SOM had n o significant effect on the ACh-induced [Ca2+](i) compared to the resp onse obtained with ACh alone. In pancreatic acinar cells of diabetic r at ACh-elicited similar magnitude of [Ca2+](i) compared to acinar cell s of normal rat. However, when the islet hormones were combined with A Ch there was no enhancement of [Ca2+](i) compared to ACh alone. The re sults indicate that the potentiation of either EFS or ACh-evoked secre tory responses by the islet hormones seem to occur only in pancreatic segments which have intact viable Islets of Langerhans and not in eith er acini and acinar cells or from the pancreas of diabetic rat. Moreov er, it is apparent that cellular Ca2+ is involved with the interaction of ACh with either INS or GLU.