Islets of Langerhans
Islets of Langerhans |
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Illustration of dog pancreas. 250x. |
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Islets of Langerhans, hemalum-eosin stain. |
Latin |
insulae pancreaticae |
The diagram shows the 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.
A porcine islet of Langerhans. The left image is a brightfield image created using hematoxylin stain; nuclei are dark circles and the acinar pancreatic tissue is darker than the islet tissue. The right image is the same section stained by immunofluorescence against insulin, indicating beta cells.
The 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 at the age of 22, the islets of Langerhans constitute approximately 1 to 2% of the mass of the pancreas. There are about one million islets in a healthy adult human pancreas, which are distributed throughout the organ; their combined mass is 1 to 1.5 grams.
In a strange foray into popular culture the islets are mentioned in the Weird Al Yankovic song Pancreas.
Cell types
Hormones produced in the islets of Langerhans are secreted directly into the blood flow by (at least) five different types of cells. In rat islets, endocrine cell subsets are distributed as follows:[1]
- Alpha cells producing glucagon (15-20% of total islet cells)
- Beta cells producing insulin and amylin (65-80%)
- Delta cells producing somatostatin (3-10%)
- PP cells producing pancreatic polypeptide (3-5%)
- Epsilon cells producing ghrelin (<1%)
It has been recognized that the cytoarchitecture of pancreatic islets differs between species.[2][3][4] In particular, while rodent islets are characterized by a predominant proportion of insulin-producing beta cells in the core of the cluster and by scarse alpha, delta and PP cells in the periphery, human islets display alpha and beta cells in close relationship with each other throughout the cluster.[2][4]
Islets can influence each other through paracrine and autocrine communication, and beta cells are coupled electrically to other beta cells (but not to other cell types).
Paracrine feedback
The paracrine feedback system of the islets of Langerhans has the following structure:[5]
- Insulin: activates beta cells and inhibits alpha cells
- Glucagon: activates alpha cells which activates beta cells and delta cells
- Somatostatin: inhibits alpha cells and beta cells
Electrical activity
Electrical activity of pancreatic islets has been studied using patch clamp techniques, and it has turned out that the behavior of cells in intact islets differs significantly from the behavior of dispersed cells.[6]
Islet transplantation as a treatment for type 1 diabetes
Islet cell transplantation has the possibility of restoring beta cell function from diabetes, offering an alternative to a complete pancreas transplantation or an artificial pancreas.
Because the beta cells in the islets of Langerhans 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 in patients with type 1 diabetes.[7][8]
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.[8]
Islet transplantation for type 1 diabetes currently requires potent immunosuppression to prevent host rejection of donor islets.[9]
An alternative source of beta cells, such insulin-producing cells derived from adult stem cells or progenitor cells would contribute overcoming the current 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.[10]
Another potential source of of beta cells may be xenotransplantation (the transfer of living cells, tissues, and/or organs from one species to another). In May 2010 JDRF announced [11] that it would be funding clinical trials of encapsulated pig islet transplantation without immuno-suppression with Living Cell Technologies. [12]
Gallery
Hormones/islet architecture
Mouse islet immunostained for pancreatic polypeptide
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Mouse islet immunostained for insulin
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Mouse islet immunostained for glucagon
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See also
References
- ↑ Elayat AA, el-Naggar MM, Tahir M (1995). "An immunocytochemical and morphometric study of the rat pancreatic islets". Journal of Anatomy 186 (Pt 3): 629–37. PMID 7559135.
- ↑ 2.0 2.1 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.
- ↑ 4.0 4.1 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. PMID 16461897.
- ↑ Wang, Michael B.; Bullock, John; Boyle, Joseph R. (2001). Physiology. Hagerstown, MD: Lippincott Williams & Wilkins. ISBN 0-683-30603-0.
- ↑ 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. 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.
- ↑ 8.0 8.1 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 of Bioscience 13: 1192–205. PMID 17981623.
- ↑ 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: 383–98. doi:10.1196/annals.1375.059. ISSN 0077-8923. PMID 17130583.
- ↑ JDRF funds research into pig islet transplantation http://www.jdrf.org.au/blog/2010/05/03/jdrf-funds-research-into-pig-islet-transplantation
- ↑ Living Cell Technologies web site: Diabecell
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