Distribution of neuropeptides and neurotransmitters and their effects on insulin and glucagon secretion in normal and diabetic rat pancreas

Abstract

Diabetes is associated with impaired insulin secretion and or derangement in the metabolic process. This is usually coupled with abnormal regulation of other pancreatic hormones because of the loss of the effects of insulin (INS) on the other pancreatic hormones such as glucagon (GLU), somatostatin (SUM) and pancreatic polypeptide (PP). The prime aim in the management of diabetes is to increase insulin secretion and to improve its action. Bioactive substances that can perform this function are important in the control of this disease. Too little information is available in the literature about the role of neuropeptides and neurotransmitters in the control of insulin and glucagon secretion from diabetic pancreatic tissues. The aim of this study is to investigate the role of the neuropeptides: vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), and substance (SP) and the neurotransmitters serotonin (5-HT), noradrenaline (NA), adrenaline (ADR), acetylcholine (ACh) and y-amino butyric acid (GABA) on INS and GLU secretion in both normal and streptozotocin-induced diabetic rats. In addition, the distribution of either the classical neurotransmitters, their enzymes or neuropeptides was also investigated for
comparison.
INS-positive cells were observed both in the central and peripheral portions of the islet of Langerhans in normal pancreas. In contrast, GLU-, SUM- and PP-immunopositive cells were located in the peripheral part of the islet of Langerhans. After the onset of diabetes, the number of INS-producing cells was reduced significantly. In contrast to this, the number of GLU-positive cells increased significantly with an abnormal pattern of distribution when compared to normal. The pattern of distribution of both SOM- and PPpositive cells was deranged in diabetes coupled with an increase in numbers when
compared to normal. The study shows that 5-HT, NA, ADR, ACh and GABA are present in the pancreas of both normal and diabetic rats. Stimulation of normal pancreatic fragments with 5-HT, NA, ADR, ACh and GABA resulted in 8.5, 5.9, 1.8, 5.0 and 6.0 fold increase in insulin secretion respectively when compared to basal. Following the induction of diabetes, NA, ACh and GABA had no significant effect on insulin output compared to the basal diabetic release. In contrast, GABA, ADR and 5-HT elicited 0.4, 0.3 and 0.4 fold decrease in insulin secretion respectively when compared to the basal diabetic release. In normal pancreas, ACh and NA increased glucagon secretion 3.4 and 3.1 times respectively when compared to basal. On the other hand, ADR and GABA had no effect on glucagon output but 5-HT elicited a 0,6 fold decrease in glucagon secretion
in comparison to basal. In diabetic pancreas, ACh , NA and ADR evoked 0.6, 0.7 and 0.4 fold decrease in glucagon secretion respectively relative to basal. In contrast, 5-HT and GABA each elicited 1.4 times increase in glucagon secretion when compared to basal. VIP, NPY and SP are present in the pancreas of normal and VIP, NPY and SP can elicite 6.1, 3.5 and 2.7 fold increase in insulin output respectively when compared to basal. In diabetic pancreas, VIP, NPY and SP are also present and when SP is applied exogenously, it resulted in a 0.4 fold decrease in insulin secretion compared to diabetic
basal. In contrast, VIP and NPY elicited 1.5 and 1.2 fold increase in insulin secretion. Stimulation of normal pancreas with VIP, NPY and SP resulted in 3.5, 2.5 and 1.5 fold increase in glucagon secretion respectively when compared to basal. In diabetic pancreas, VIP elicited 1.3 fold increase in glucagon secretion above basal. In contrast NPY evoked 0.7- while SP induced 0.3-fold decrease in glucagon secretion when compared to diabetic basal values. In conclusion neuropeptides and neurotransmitters are widely distributed in the pancreas of both normal and diabetic rats and they have potent secretagogue effect on normal pancreatic endocrine secretion. The effect is, however, impaired in diabetes. The result of this study have provided a wide insight into the role of neuropeptides and neurotransmitters on insulin and glucagon secretion from normal and diabetic pancreas.