The pancreatic islets or islets of Langerhans are the regions of the pancreas that contain its endocrine (hormone-producing) cells, discovered in 1869 by German pathological anatomist Paul Langerhans. The pancreatic islets constitute 1 to 2% of the pancreas volume and receive 10–15% of its blood flow. The pancreatic islets are arranged in density routes throughout the human pancreas, and are important in the metabolism of glucose.
There are about 3 million islets distributed in the form of density routes throughout the pancreas of a healthy adult human, each of which measures an average of about 0.1 mm (109 µm) in diameter.:914 Each is separated from the surrounding pancreatic tissue by a thin fibrous connective tissue capsule which is continuous with the fibrous connective tissue that is interwoven throughout the rest of the pancreas.:914
Hormones produced in the pancreatic islets are secreted directly into the blood flow by (at least) five types of cells. In rat islets, endocrine cell subsets are distributed as follows:
It has been recognized that the cytoarchitecture of pancreatic islets differs between species.
In particular, while rodent islets are characterized by a predominant proportion of insulin-producing beta cells in the core of the cluster and by scarce alpha, delta and PP cells in the periphery, human islets display alpha and beta cells in close relationship with each other throughout the cluster.
Islets can influence each other through paracrine and autocrine communication, and beta cells are coupled electrically to six to seven other beta cells (but not to other cell types).
A pancreatic islet, stained.
A pancreatic islet, showing alpha cells
A pancreatic islet, showing beta cells.
The paracrine feedback system of the pancreatic islets has the following structure:
Glucose/Insulin: activates beta cells and inhibits alpha cells
Glycogen/Glucagon: activates alpha cells which activates beta cells and delta cells
Somatostatin: inhibits alpha cells and beta cells
A large number of G protein-coupled receptors (GPCRs) regulate the secretion of insulin, glucagon and somatostatin from pancreatic islets, and some of these GPCRs are the targets of drugs used to treat type-2 diabetes (ref GLP-1 receptor agonists, DPPIV inhibitors).
Mouse islet immunostained for pancreatic polypeptide
Mouse islet immunostained for insulin
Mouse islet immunostained for glucagon
Electrical activity of pancreatic islets has been studied using patch clamp techniques. It has turned out that the behavior of cells in intact islets differs significantly from the behavior of dispersed cells.
The beta cells of the pancreatic islets secrete insulin, and so play a significant role in diabetes. It is thought that they are destroyed by immune assaults. However, there are also indications that beta cells have not been destroyed but have only become non-functional.
Because the beta cells in the pancreatic islets are selectively destroyed by an autoimmune process in type 1 diabetes, clinicians and researchers are actively pursuing islet transplantation as a means of restoring physiological beta cell function, which would offer an alternative to a complete pancreas transplant or artificial pancreas. Islet transplantation emerged as a viable option for the treatment of insulin requiring diabetes in the early 1970s with steady progress over the last three decades. Recent clinical trials have shown that insulin independence and improved metabolic control can be reproducibly obtained after transplantation of cadaveric donor islets into patients with unstable type 1 diabetes.
An alternative source of beta cells, such insulin-producing cells derived from adult stem cells or progenitor cells would contribute to overcoming the shortage of donor organs for transplantation. The field of regenerative medicine is rapidly evolving and offers great hope for the nearest future. However, type 1 diabetes is the result of the autoimmune destruction of beta cells in the pancreas. Therefore, an effective cure will require a sequential, integrated approach that combines adequate and safe immune interventions with beta cell regenerative approaches. It has also been demonstrated that alpha cells can spontaneously switch fate and transdifferentiate into beta cells in both healthy and diabetic human and mouse pancreatic islets, a possible future source for beta cell regeneration. In fact, it has been found that islet morphology and endocrine differentiation are directly related. Endocrine progenitor cells differentiate by migrating in cohesion and forming bud-like islet precursors, or "peninsulas", in which alpha cells constitute the peninsular outer layer and beta cells form later beneath them.
Pancreatic islets, the lighter tissue among the darker, acinar pancreatic tissue, hemalum-eosinstain.
Illustration of dog pancreas. 250x.
Structural differences between rat islets (top) and humans islets (bottom) as well as the ventral part (left) and the dorsal part (right) of the pancreas. Different cell types are colour-coded. Rodent islets, unlike the human ones, show the characteristic insulin core.
^Pour, Parviz M.; Standop, Jens; Batra, Surinder K. (January 2002). "Are islet cells the gatekeepers of the pancreas?". Pancreatology. 2 (5): 440–448. doi:10.1159/000064718. PMID12378111.
^ abSleisenger, edited by Mark Feldman, Lawrence S. Friedman, Lawrence J. Brandt; consulting editor, Marvin H. (2009). Sleisenger & Fordtran's gastrointestinal and liver disease pathophysiology, diagnosis, management (9th ed.). St. Louis, Missouri: MD Consult. ISBN978-1-4160-6189-2.CS1 maint: extra text: authors list (link)
^ abBrissova M, Fowler MJ, Nicholson WE, Chu A, Hirshberg B, Harlan DM, Powers AC (2005). "Assessment of human pancreatic islet architecture and composition by laser scanning confocal microscopy". Journal of Histochemistry and Cytochemistry. 53 (9): 1087–97. doi:10.1369/jhc.5C6684.2005. PMID15923354.
^Ichii H, Inverardi L, Pileggi A, Molano RD, Cabrera O, Caicedo A, Messinger S, Kuroda Y, Berggren PO, Ricordi C (2005). "A novel method for the assessment of cellular composition and beta-cell viability in human islet preparations". American Journal of Transplantation. 5 (7): 1635–45. CiteSeerX10.1.1.578.5893. doi:10.1111/j.1600-6143.2005.00913.x. PMID15943621.
^Kelly, Catriona; McClenaghan, Neville H.; Flatt, Peter R. (2011). "Role of islet structure and cellular interactions in the control of insulin secretion". Islets. 3 (2): 41–47. doi:10.4161/isl.3.2.14805. PMID21372635.
^Wang, Michael B.; Bullock, John; Boyle, Joseph R. (2001). Physiology. Hagerstown, MD: Lippincott Williams & Wilkins. p. 391. ISBN978-0-683-30603-3.
^"An atlas and functional analysis of G-protein coupled receptors in human islets of Langerhans.Amisten S, Salehi A, Rorsman P, Jones PM, Persaud SJ., Pharmacol Ther. 2013 May 18. PMID23694765
^ abHogan A, Pileggi A, Ricordi C (2008). "Transplantation: current developments and future directions; the future of clinical islet transplantation as a cure for diabetes". Frontiers in Bioscience. 13 (13): 1192–205. doi:10.2741/2755. PMID17981623.