The pancreatic islets or islets of Langerhans are the regions of the pancreas that contain its endocrine (i.e., 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.
Pancreatic islet (mouse) in its typical proximity to a blood vessel; insulin in red, nuclei in blue.
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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 The combined mass of the islets is 2 grams. Islets of Langerhans can also form superstructures called islet clusters surrounding large blood vessels. The roundness of islets along the pancreas has also been quantified as an index of sphericity. Islets closest to the spherical form are mainly found in the tail of the pancreas, whereas the least-spherical islets are found in the neck of the pancreas.
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:
- Alpha cells producing glucagon (20% of total islet cells)
- Beta cells producing insulin and amylin (≈70%)
- Delta cells producing somatostatin (<10%)
- PP cells (gamma cells or F cells) producing pancreatic polypeptide (<5%)
- Epsilon cells producing ghrelin (<1%)
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.
- 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).
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.
The islet density routes throughout the healthy human pancreas
- Langerhans P (1869). "Beitrage zur mikroscopischen anatomie der bauchspeichel druse". Inaugural-dissertation. Berlin: Gustav Lange.
- Ionescu-Tirgoviste, Constantin; Gagniuc, Paul A.; Gubceac, Elvira; Mardare, Liliana; Popescu, Irinel; Dima, Simona; Militaru, Manuella (2015-09-29). "A 3D map of the islet routes throughout the healthy human pancreas". Scientific Reports. 5. doi:10.1038/srep14634. PMC . PMID 26417671.
- Barrett KE, Boitano S, Barman SM, Brooks HL. Ganong's review of medical physiology (23 ed.). McGraw Hill Medical. p. 316. ISBN 978-0-07-160568-7.
- Functional Anatomy of the Endocrine Pancreas
- 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.
- Sleisenger, 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. ISBN 978-1-4160-6189-2.
- Elayat AA; el-Naggar MM; Tahir M; Bassam dahrouj (1995). "An immunocytochemical and morphometric study of the rat pancreatic islets". Journal of Anatomy. 186. (Pt 3) (Pt 3): 629–37. PMC . PMID 7559135.
- Brissova 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. PMID 15923354.
- 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. doi:10.1111/j.1600-6143.2005.00913.x. PMID 15943621.
- Cabrera O, Berman DM, Kenyon NS, Ricordi C, Berggren PO, Caicedo A (2006). "The unique cytoarchitecture of human pancreatic islets has implications for islet cell function". Proceedings of the National Academy of Sciences of the United States of America. 103 (7): 2334–9. doi:10.1073/pnas.0510790103. ISSN 1091-6490. PMC . PMID 16461897.
- 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.
- Wang, Michael B.; Bullock, John; Boyle, Joseph R. (2001). Physiology. Hagerstown, MD: Lippincott Williams & Wilkins. p. 391. ISBN 0-683-30603-0.
- "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. PMID 23694765
- Pérez-Armendariz M, Roy C, Spray DC, Bennett MV (1991). "Biophysical properties of gap junctions between freshly dispersed pairs of mouse pancreatic beta cells". Biophysical Journal. 59 (1): 76–92. doi:10.1016/S0006-3495(91)82200-7. PMC . PMID 2015391.
- Meloche RM (2007). "Transplantation for the treatment of type 1 diabetes". World Journal of Gastroenterology. 13 (47): 6347–55. doi:10.3748/wjg.13.6347. PMID 18081223.
- Hogan 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. PMID 17981623.
- Piemonti L, Pileggi A (2013). "25 Years of the Ricordi Automated Method for Islet Isolation". CellR4. 1 (1): 8–22.
- Chatenoud L (2008). "Chemical immunosuppression in islet transplantation—friend or foe?". New England Journal of Medicine. 358 (11): 1192–3. doi:10.1056/NEJMcibr0708067. ISSN 0028-4793. PMID 18337609.
- Pileggi A, Cobianchi L, Inverardi L, Ricordi C (2006). "Overcoming the challenges now limiting islet transplantation: a sequential, integrated approach". Annals of the New York Academy of Sciences. 1079 (1): 383–98. doi:10.1196/annals.1375.059. ISSN 0077-8923. PMID 17130583.
- van der Meulen, T.; Mawla, A.M.; DiGruccio, M.R.; Adams, M.W.; Nies, V.; Dolleman, S.; Liu, S.; Ackermann, A.M.; Caceres, E.; Hunter, A.E.; Kaestner, K.H.; Donaldson, C.J.; Huising, M.O. (2017). "Virgin Beta Cells Persist throughout Life at a Neogenic Niche within Pancreatic Islets". Cell Metabolism. 25 (4): 911–926. doi:10.1016/j.cmet.2017.03.017. PMID 28380380.