Regulation of Pancreatic Function - Research Paper Example

Regulation of Pancreatic Function The pancreas is an organ that performs both exocrine andendocrine functions. The endocrine functions include the production of insulin, glucagon, somatostatin and pancreatic polypeptides by the islet cells. This research paper will focus on the regulation of the exocrine function. The exocrine function involves the release of digestive enzymes through the pancreatic duct. The research specifically handles the regulation of the acinar cells. These cells are responsible for the release of zymogens that play a critical role in digestion. The paper highlights the presence of receptors and secretagogues that initiate the secretion of the zymogens. The main secreatagogues include the acetylcholine, cholecystokinin and other associated peptides. The paper also describes the mechanism of calcium ion signalling pathway in regulating secretion. Moreover, the paper provides details of the secretion mechanism, detailing all the mechanism and their regulation. Regulation of the pancreatic function in the acinar cells is complex, and scientists are yet to describe all the mechanisms in depth. Introduction The functioning of the pancreas presents complex pathways. The organ exhibits both exocrine and endocrine functions. The fact that the peculiar organ exhibits both of these function s has intrigued scientists to unveil the regulatory mechanism that govern its function. As expected, the organ has both neural and hormonal forms of regulation. Pancreatic duct cells secrete a combination of fluid and bicarbonate ions responsible for the neutralization of gastric contents in the duodenum. Since this secretion involves a duct, it defines the exocrine function of the organ. On the other hand, the pancreas consists of four types of endocrine cells that secrete varying hormones. The alpha cells are responsible for glucagon secretion, while the beta cells produce insulin. In addition, there is production of somatostatin from delta cells, and pancreatic polypeptide from PP cells. Structural studies of the pancreas indicate an assembly of the endocrine cells in the islets. This paper will highlight the regulatory mechanisms of the acinar cells responsible for the secretion of the juices that play a role in digestion. Acinar cells of the pancreas bear the responsibility of synthesis and secretion of the numerous enzymes that aid in digestion of nutrients in the small intestine lumen. The critical function played by the digestive enzymes necessitates the availability of both short and long-term regulation. Such regulation serves to ensure a supply of the enzymes after food intake. The regulation process requires the availability of receptors and secretagogues that initiate the secretion process (Husain, and Thrower 466-7). Receptors and Secretagogues The primary secretagogues responsible for initiating secretions from acinar cells are acetylcholine and cholecystokinin (CCK) (Wu et al 642). The vagal postganglionic neurons are responsible for the release of acetylcholine. On the other hand, CCK comes from the intestinal endocrine cells. Moreover, secretin, a secretagogue for initiating secretion in duct cells also plays a critical role in the acinar cells. There are numerous receptors for hormones, growth factors, and neurotransmitters in the acinar cells. Studies reveal that activity on these receptors influence the secretion patterns of the acinar cells. CCK has the potential of activating CCK receptors on the vagal afferent endings. Scientists have described the mechanism responsible for this activation as paracrine. Other studies have highlighted that CCK advances to the blood and exerts control on the contractile mechanisms of the gall bladder. This triggers emptying of the bladder. Animal studies have established that CCK receptors play a vital role in the acinar cells of rodents. However, studies are yet to confirm the role of the same in humans. In addition, the acinar cells exhibit effects of other peptides responsible for regulation. One of these is an incretin identified as GLP-1. The distal small intestines are responsible for its production. Due to its proven effect on the islets involved in endocrine purposes, scientists have postulated that it plays an additional role in exocrine functions. Signaling Pathways Intracellular Ca2+ Signaling Intracellular calcium ions register an increase each time there is need for digestive enzymes. The increase of intracellular calcium ions serves to activate the production of digestive enzymes from the acinar cells (Yamasaki et al 7236). The paradigm involving calcium cells signaling brings into action the receptors of CCK, acetylcholine and an additional protein molecule called bombesin. The paradigm utilizes a heterotrimeric collection of G proteins, leading to the production of messengers responsible for the release of intracellular calcium ions (Harikumar et al 11773). One of the messengers leading to the production of calcium ions is inositol triphosphate (IP3); usually released under the influence of phospholipase C. cyclic ADP ribose and nicotinic acid adenine dinucleotide (NAADP) are the other messengers responsible for initiating the release of calcium ions. IP3 exerts its effects on the receptors in the endoplasmic reticulum while the action of NAADP is on the lysosomes and endosomes. A continuous influx of calcium ions in the membrane channels occurs with a decrease necessitated a greater influx. Recent studies have embarked on describing the mechanisms involved in the calcium ion signaling and the structure of the channels (Brailoiu et al 208). Exocytosis of Digestive Enzymes Understanding the signaling pathway of calcium ions provides a platform for delving deeper to describe the detailed process of secretion. Scientists have described the presence of G proteins exhibiting a small size that actively participate in numerous steps of the secretion process. The secretagogues described above paper to have a function in activating the different families of the G proteins (Williams 1337). The Rho and Rac families belong to this group of G proteins. The activation of these proteins causes cytoskeletal reorganization. Moreover, they are responsible for the secretion of amylase, but do not alter the calcium ion mobilization. An additional protein family identified on some zymogens is the Rab group. Although recent studies have provided hints on the activation processes of these protein families, their effects and their fate after function, there is need for clarification (Sabbatini et al 23888). Postulations by some scientists indicate that the effect of some secretogogues stretches to this point. Moreover, the protein kinase C that exhibits multiple isoforms plays a role in the secretion process. The different isoforms perform varying functions as described in rat studies. There is an inhibition and activation mechanism that regulates the presence of the crucial protein Kinase C. Moreover, myosin II also takes part in regulating the process of secretion. One of its variant forms Myosin II A occurs in the apical region of the cells. This molecule requires phosphorylation, a process mediated by the activated secretogogues. Myosin ensures that the fusion pore remains open hence easy release of the digestive enzymes. It is possible that other Src kinases play active roles through the phosphorylation of actin. Since this occurs specifically, it causes a redistribution process of actin initiating secretion. An alternative process of secretion brings into action lysosomal vesicles (Singer, and Niebergall-Roth 5). The fact that a certain protein exhibited the potential of promoting the translocation of a lysosomal marker in an experiment served as evidence that the use of lysosomal vesicles was one of the mechanisms involved in secretion. There are other regulatory mechanisms that scientists are still trying to unveil. Moreover, the differentiation and degeneration regulatory mechanisms are of interest in understanding the secretion process. Additional regulatory procedures ensure that the digestive enzymes secreted are in their inactive forms. As described above, the organ exhibits both exocrine and endocrine functions. The fact that the peculiar organ exhibits both of these function s has intrigued scientists to unveil the regulatory mechanism that govern its function. As expected, the organ has both neural and hormonal forms of regulation. Secretagogues play a significant role in regulating the function of the pancreas. The calcium ion signalling is one of the important signalling pathways. Moreover, multiple mechanisms explaining how secretion of zymogens occurs exist. Work Cited Brailoiu, Eugen et al. “Essential requirement for two-pore channel 1 in NAADP-mediated calcium signaling”. J Cell Biol. 2009;186:201–209. Web. 6 Mar. 2013. Harikumar, Kaleeckal et al. “Molecular basis of association of receptor activity-modifying protein3 with the family B G protein-coupled secretin receptor”. Biochemistry. 2009;48:11773–11785. Web. 6 Mar. 2013. Husain, Sohail, and Thrower, Edwin. “Molecular and cellular regulation of pancreatic acinar cell function”. Curr Opin Gastroenterol. 2009;25:466–471. Web. 6 Mar. 2013. Sabbatini, Maria et al.“Rap1 activation plays a regulatory role in pancreatic amylase secretion”. J Biol Chem. 2008;283:23884–23894. Web. 6 Mar. 2013. Singer, Manfred, and Niebergall-Roth Elke. “Secretion from acinar cells of the exocrine pancreas: role of enteropancreatic reflexes and cholecystokinin”. Cell Biol Int. 2009;33(1):1–9. Web. 6 Mar. 2013. Williams, John. “Stimulus-secretion coupling in pancreatic acinar cells”. In: Johnson LR, editor. Physiology of the Digestive Tract. 4th ed. New York: Academic Press; 2006. pp. 1337–1369. Web. 6 Mar. 2013. Wu ,Vincent et al. “Effects of cholecystokinin-58 on type 1 cholecystokinin receptor function and regulation”. Am J Physiol Gastrointest Liver Physiol. 2008;295:G641–G647. Web. 6 Mar. 2013. Yamasaki, Michiko et al. “Organelle selection determines agonist-specific Ca2+ signals in pancreatic acinar and beta cells”. J Biol Chem. 2004;279:7234–7240. Web. 6 Mar. 2013. Read More