Pankreas Fizyolojisi ve Sekresyonları
Özet
Pankreas, hem endokrin hem de ekzokrin fonksiyonlara sahip, enerji metabolizmasında kritik rol oynayan hayati bir salgı bezidir. Endokrin fonksiyonlar, Langerhans adacıklarındaki beta hücrelerinden salgılanan ve kan şekerini düşüren insülin ile alfa hücrelerinden salgılanan ve kan şekerini yükselten glukagon hormonları tarafından yönetilir; ayrıca somatostatin, ghrelin ve pankreatik polipeptit gibi düzenleyiciler de bu sürece katılır. İnsülin, glikozun hücre içine taşınmasını sağlayıp glikojen sentezini artırırken, glukagon tam tersi bir etkiyle glikojen yıkımını ve glikoneogenezi tetikler. Ekzokrin bölüm ise sindirim için gerekli olan amilaz, lipaz ve tripsinojen gibi enzimleri içeren alkali bir sıvı salgılayarak karbonhidrat, yağ ve proteinlerin parçalanmasını sağlar. Bu salgı süreci sefalik, gastrik ve intestinal fazlar aracılığıyla vagal uyarım, kolesistokinin ve sekretin hormonları tarafından titizlikle kontrol edilir. Pankreasın kendi ürettiği proteolitik enzimlerden zarar görmemesi için bu enzimler inaktif zimogenler olarak salgılanır ve tripsin inhibitörleri ile korunur. Hem hormonal hem de sinirsel kontrol mekanizmaları, besinlerin verimli bir şekilde sindirilmesini ve metabolik dengenin korunmasını sağlar.
The pancreas is a vital gland with both endocrine and exocrine functions that play a critical role in energy metabolism, where endocrine functions are managed by insulin, which lowers blood sugar and is secreted from beta cells in the Islets of Langerhans, and glucagon, which raises blood sugar and is secreted from alpha cells, alongside regulators like somatostatin, ghrelin, and pancreatic polypeptide. While insulin facilitates the transport of glucose into cells and increases glycogen synthesis, glucagon exerts the opposite effect by triggering glycogen breakdown and gluconeogenesis; meanwhile, the exocrine section secretes an alkaline fluid containing enzymes such as amylase, lipase, and trypsinogen necessary for digestion to ensure the breakdown of carbohydrates, fats, and proteins. This secretion process is meticulously controlled by vagal stimulation and the hormones cholecystokinin and secretin through cephalic, gastric, and intestinal phases, and to prevent the pancreas from being damaged by its own proteolytic enzymes, these enzymes are secreted as inactive zymogens and protected by trypsin inhibitors. Both hormonal and neural control mechanisms ensure the efficient digestion of nutrients and the maintenance of metabolic balance.
Referanslar
Arthur C. Guyton, Guyton and Hall Textbook of Medical Physiology, 13nd Edition, 2017
Robertson R P. Pancreatic beta cell function. Dec. 2021
Yasuda K, Yamada Y, Inagaki N, et al. Expression of GLUT1 and GLUT2 glucose transporter isoforms in rat islets of Langerhans and their regulation by glucose. Diabetes 1992 Jan;41(1):76-81
Liang Y, Cushman SM, Whitesell RR, Matschinsky FM GLUT1 is adequate for glucose uptake in GLUT2-deficient insulin-releasing beta-cells. Horm Metab Res. Jun;29(6):255-60.
Matschinsky F, Liang Y, Kesavan P, et al. Glucokinase as pancreatic beta cell glucose sensor and diabetes gene . J Clin Inves. 1993 Nov;92(5):2092-8.
Matschinsky F M. Banting Lecture 1995. A lesson in metabolic regulation inspired by the glucokinase glucose sensor paradigm. Diabetes. 1996 Feb;45(2):223-41.
Froguel P, Zouali H, Vionnet N, et al. Familial hyperglycemia due to mutations in glucokinase. Definition of a subtype of diabetes mellitusN Engl J Med. 1993 Mar 11;328(10):697-702.
Grupe A, Hultgren B, Ryan A, et al. Transgenic knockouts reveal a critical requirement for pancreatic beta cell glucokinase in maintaining glucose homeostasisCell. 1995 Oct 6;83(1):69-78.
Terauchi Y, Sakura H, Yasuda K, et al. Pancreatic beta-cell-specific targeted disruption of glucokinase gene. Diabetes mellitus due to defective insulin secretion to glucose J Biol Chem. 1995 Dec 22;270(51):30253-6.
Koster JC, Marshall BA, Ensor N, et al. Targeted overactivity of beta cell K(ATP) channels induces profound neonatal diabetes. Cell. 2000 Mar 17;100(6):645-54.
Aguilar-Bryan L, Nichols CG, Wechsler SW, et al. Cloning of the beta cell high-affinity sulfonylurea receptor: a regulator of insulin secretion. Science. 1995 Apr 21;268(5209):423-6
Sperling MA, Menon RK. Hyperinsulinemic hypoglycemia of infancy. Recent insights into ATP-sensitive potassium channels, sulfonylurea receptors, molecular mechanisms, and treatment. Endocrinol Metab Clin North Am. 1999 Dec;28(4):695-708, vii.
Pessin JE, Saltiel AR. Signaling pathways in insulin action: molecular targets of insulin resistance. J Clin Invest. 2000 Jul;106(2):165-9.
Kido Y, Nakae J, Accili D. Clinical review 125: The insulin receptor and its cellular targets. J Clin Endocrinol Metab. 2001 Mar;86(3):972-9.
Ramnanan CJ, Edgerton DS, Rivera N, et al. Molecular characterization of insulin-mediated suppression of hepatic glucose production in vivo. Diabetes. 2010 Jun;59(6):1302-11.
Philippe J. Insulin regulation of the glucagon gene is mediated by an insulin-responsive DNA element.Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7224-7.
Kahn BB. Lilly lecture 1995. Glucose transport: pivotal step in insulin action. Diabetes. 1996 Nov;45(11):1644-54.
Farese RV Jr, Yost TJ, Eckel RH. Tissue-specific regulation of lipoprotein lipase activity by insulin/glucose in normal-weight humans. Metabolism. 1991 Feb;40(2):214-6.
Fielding BA, Frayn KN. Lipoprotein lipase and the disposition of dietary fatty acids. Br J Nutr. 1998 Dec;80(6):495-502.
Vaughan M, Steinberg D, Stanley S. Activation and inactivation of lipase in homogenates of adipose tissue. Life Sci. 1965 May;4(10):1077-83.
Strålfors P, Björgell P, Belfrage P. Hormonal regulation of hormone-sensitive lipase in intact adipocytes: identification of phosphorylated sites and effects on the phosphorylation by lipolytic hormones and insulin. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3317-21.
Zimmermann R, Lass A, Haemmerle G, Zechner R. Fate of fat: the role of adipose triglyceride lipase in lipolysis. Biochim Biophys Acta. 2009 Jun;1791(6):494-500.
Lass A, Zimmermann R, Oberer M, Zechner R. Lipolysis - a highly regulated multi-enzyme complex mediates the catabolism of cellular fat stores. Prog Lipid Res. 2011 Jan;50(1):14-27.
Enoksson S, Degerman E, Hagström-Toft E, et al. Various phosphodiesterase subtypes mediate the in vivo antilipolytic effect of insulin on adipose tissue and skeletal muscle in man. Diabetologia. 1998 May;41(5):560-8.
Strålfors P, Honnor RC. Insulin-induced dephosphorylation of hormone-sensitive lipase. Correlation with lipolysis and cAMP-dependent protein kinase activity. Eur J Biochem. 1989 Jun 15;182(2):379-85.
Aoun E, Muddana V, Papachristou GI, Whitcomb DC. SPINK1 N34S is strongly associated with recurrent acute pancreatitis but is not a risk factor for the first or sentinel acute pancreatitis event. Am J Gastroenterol. 2010;105(2):446-51.
Apte MV, Pirola RC, Wilson JS Mechanisms of alcoholic pancreatitis. J Gastroenterol Hepatol. 2010;25 (12):1816-26.
Chandra R, Liddle RA. Modulation of pancreatic exocrine and endocrine secretion.Curr Opin Gastroenterol. 2013;29(5):517-22.
Chandra R, Liddle RA. Neural and hormonal regulation of pancreatic secretion. Curr Opin Gastroenterol. 2009;25(5):441-6
Chandra R, Liddle RA. Recent advances in pancreatic endocrine and exocrine secretion. Curr Opin Gastroenterol. 2011;27(5):439-43.
