Glucagon Secreting Cells Responds to Insulin Secretion In vitro Using Immunocytochemistry

In the present study, pancreas of rats were dissected and transferred to HEPES buffer (25 mM, pH 7.4). The control tissue pieces were kept in culture medium for one hour and the treated tissues were kept in same medium for 30 minutes and incubated with Insulin (10 nm and 100 nm) for another half hour, then tissues were transferred to Bouin‘s fixative (overnight at 40 ° Cc), cryosectioned (15 µm at -16 0 c) and subjected to immunocytochemical labeling with antibodies against Glucagon

Recent Progress in the Use of Glucagon and Glucagon Receptor Antagonists in the Treatment of Diabetes Mellitus

Glucagon is an important pancreatic hormone, released into blood circulation by alpha cells of the islet of Langerhans. Glucagon induces gluconeogenesis and glycogenolysis in hepatocytes, leading to an increase in hepatic glucose production and subsequently hyperglycemia in susceptible individuals. Hyperglucagonemia is a constant feature in patients with T2DM. A number of bioactive agents that can block glucagon receptor have been identified. These glucagon receptor antagonists can reduce the hyperglycemia associated with exogenous glucagon administration in normal as well as diabetic subjects. Glucagon receptor antagonists include isoserine and beta-alanine derivatives, bicyclic 19-residue peptide BI-32169, Des-His1-[Glu9] glucagon amide and related compounds, 5-hydroxyalkyl-4-phenylpyridines, N-[3-cano-6- (1,1 dimethylpropyl)-4,5,6,7-tetrahydro-1-benzothien-2-yl]-2-ethylbutamide, Skyrin and NNC 250926. The absorption, dosage, catabolism, excretion and medicinal chemistry of these agents are the subject of this review. It emphasizes the role of glucagon in glucose homeostasis and how it could be applied as a novel tool for the management of diabetes mellitus by blocking its receptors with either monoclonal antibodies, peptide and non-peptide antagonists or gene knockout techniques

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

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

Neurodegeneration and Sensorimotor Deficits in the Mouse Model of Traumatic Brain Injury

Traumatic brain injury (TBI) can result in persistent sensorimotor and cognitive deficits, which occur through a cascade of deleterious pathophysiological events over time. In this study, we investigated the hypothesis that neurodegeneration caused by TBI leads to impairments in sensorimotor function. TBI induces the activation of the caspase-3 enzyme, which triggers cell apoptosis in an in vivo model of fluid percussion injury (FPI). We analyzed caspase-3 mediated apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and poly (ADP-ribose) polymerase (PARP) and annexin V western blotting. We correlated the neurodegeneration with sensorimotor deficits by conducting the animal behavioral tests including grid walk, balance beam, the inverted screen test, and the climb test. Our study demonstrated that the excess cell death or neurodegeneration correlated with the neuronal dysfunction and sensorimotor impairments associated with TBI