The
islets of Langerhans are the regions of the
pancreasThe pancreas is a gland organ in the digestive and endocrine system of vertebrates. It is both an endocrine gland producing several important hormones, including insulin, glucagon, and somatostatin, as well as an exocrine gland, secreting pancreatic juice containing digestive enzymes that pass to...
that contain its endocrine (i.e., hormone-producing) cells. Discovered in 1869 by German pathological anatomist
Paul LangerhansPaul Langerhans was a German pathologist, physiologist biologist.-Eponymous terms:* Islets of Langerhans - Pancreatic cells which produce insulin...
, 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.
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:
- Alpha cell
Alpha cells are endocrine cells in the islets of Langerhans of the pancreas. They make up 33-46% of the human islet cells and are responsible for synthesizing and secreting the peptide hormone glucagon, which elevates the glucose levels in the blood....
s producing glucagonGlucagon is an important hormone involved in carbohydrate metabolism. Produced by the pancreas, it is released when blood glucose levels start to fall too low, causing the liver to convert stored glycogen into glucose and release it into the bloodstream, raising blood glucose levels and ultimately...
(15-20% of total islet cells)
- Beta cell
right|thumbnail|300px|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...
s producing insulinInsulin is a hormone that has extensive effects on metabolism and other body functions, such as vascular compliance. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle, and stopping use of fat as an energy...
and amylinAmylin, or Islet Amyloid Polypeptide , is a 37-residue peptide hormone secreted by pancreatic β-cells at the same time as insulin . -Clinical significance:...
(65-80%)
- Delta cell
Not to be confused with D_batteryDelta cells are somatostatin producing cells.They can be found in the stomach, intestine and the Islets of Langerhans in the pancreas....
s producing somatostatinSomatostatin is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G-protein-coupled somatostatin receptors and inhibition of the release of numerous secondary hormones.Somatostatin...
(3-10%)
- PP cell
PP cells are pancreatic polypeptide producing cells in the islets of Langerhans in the pancreas. They are very few in number and are polygonal in shape....
s producing pancreatic polypeptidePancreatic polypeptide is a polypeptide secreted by PP cells in the endocrine pancreas predominantly in the head of the pancreas. It consists of 36 amino acids and has molecular weight about 4200 Da....
(3-5%)
- Epsilon cell
Epsilon cells are endocrine cells found in the Islets of Langerhans and produce the hormone ghrelin. They were recently discovered in mice.- References :http://www.ihop-net.org/UniPub/iHOP/pm/10257219.html?pmid=14970313...
s producing ghrelinGhrelin is a hormone produced mainly by P/D1 cells lining the fundus of the human stomach and epsilon cells of the pancreas that stimulates hunger. Ghrelin levels increase before meals and decrease after meals. It is considered the counterpart of the hormone leptin, produced by adipose tissue,...
(<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 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.
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:
- 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 clampThe patch clamp technique is a laboratory technique in electrophysiology that allows the study of single or multiple ion channels in cells. The technique can be applied to a wide variety of cells, but is especially useful in the study of excitable cells such as neurons, cardiomyocytes, muscle...
techniques, and it has turned out that the behavior of cells in intact islets differs significantly from the behavior of dispersed cells.
As a treatment for type 1 diabetes
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.
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 diabetesBrittle diabetes, also known as unstable diabetes or labile diabetes, refers to a type of insulin-dependent diabetes characterized by dramatic and recurrent swings in glucose levels, often occurring for no apparent reason....
.
Islet transplantation for type 1 diabetes currently requires potent
immunosuppressionImmunosuppression involves an act that reduces the activation or efficacy of the immune system. Some portions of the immune system itself have immuno-suppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reaction to treatment of other conditions...
to prevent host
rejectionThe word "rejection" was first used in 1415. The original meaning was "to throw" or "to throw back".Rejection may mean:* Social rejection, in psychology, an interpersonal situation that occurs when a person or group of people exclude an individual from a social relationship* Transplant rejection,...
of donor islets.
Rachel Harris, islet cell recipient, was transplanted at the Diabetes Research Institute in Miami, Florida. In February 2004, Rachel became the world's longest surviving insulin-free diabetic according to the
Miami Herald.
An alternative source of
beta cellright|thumbnail|300px|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...
s, such an islets derived from
adult stem cellAdult stem cells are undifferentiated cells, found throughout the body after embryonic development, that multiply by cell division to replenish dying cells and regenerate damaged tissues...
s or
progenitor cellLike stem cells, progenitor cells have a capacity to differentiate into a specific type of cell. In contrast to stem cells, however, they are already far more specific: they are pushed to differentiate into their "target" cell...
s of a diabetic 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.
Transplantation
Islet cell transplantation has the possibility of restoring beta cells and curing diabetes, offering an alternative to a complete
pancreas transplantationA pancreas transplant is an organ transplant that involves implanting a healthy pancreas into a person who usually has diabetes. Because the pancreas is a vital organ, performing functions necessary in the digestion process, the recipient's native pancreas is left in place, and the donated...
or an
artificial pancreasThe artificial pancreas is a technology in development to help people with diabetes automatically control their blood glucose level by providing the substitute endocrine functionality of a healthy pancreas....
.
The Chicago Project headed at University of Illinois at Chicago Medical Center is investigating ways to regenerate beta cells
in vivo. With that being said, beta cells experience
apoptosisApoptosis is the process of programmed cell death that may occur in multicellular organisms. Programmed cell death involves a series of biochemical events leading to a characteristic cell morphology and death; in more specific terms, a series of biochemical events that lead to a variety of...
early and thus are destroyed within a normal-functioning pancreas. The source of this seems to come from the transfer of Pander (
FAM3BProtein FAM3B is a protein that in humans is encoded by the FAM3B gene.-Further reading:...
), a gene that works by attaching to
RNARibonucleic acid is a biologically important type of molecule that consists of a long chain of nucleotide units. Each nucleotide consists of a nitrogenous base, a ribose sugar, and a phosphate...
.
Pander, when active, causes the beta cells to be blocked at
S phaseThe S phase, short for synthesis phase, is a period in the cell cycle during interphase, between G1 phase and the G2 phase. Following G1, the cell enters the S stage, when DNA synthesis or replication occurs. At the beginning of the S stage, each chromosome is...
, which induces apoptosis. This loss of beta cell mass eventually leads to a loss of most of the transplanted beta cells.
External links
- "Pancreas, human - H&E", Blue Histology - Accessory Digestive Glands, School of Anatomy and Human Biology, The University of Western Australia
The University of Western Australia is the oldest university in the state of Western Australia. Established in February 1911, it is the only university in the state to be a member of the prestigious Group of Eight, as well as the Sandstone universities. The University was established under and is...