islets of Langerhans

This photograph shows a mouse pancreatic islet, an often spherical group of hormone-producing cells. Insulin is labelled here in green, glucagon in red, and the nuclei in blue.

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.

Islets of Langerhans, hemalum-eosin stain.

Illustration of dog pancreas. 250x.

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.

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]

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.^[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] 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.^[10]

An alternative source of beta cells, such an islets derived from adult stem cells or progenitor cells 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.^[11]

Transplantation

Islet cell transplantation has the possibility of restoring beta cells and curing diabetes, offering an alternative to a complete pancreas transplantation or an artificial 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 apoptosis early and thus are destroyed within a normal-functioning pancreas. The source of this seems to come from the transfer of Pander (FAM3B), a gene that works by attaching to RNA.^[12] Pander, when active, causes the beta cells to be blocked at S phase, which induces apoptosis. This loss of beta cell mass eventually leads to a loss of most of the transplanted beta cells.

Gallery

Hormones/islet architecture

Mouse islet immunostained for pancreatic polypeptide

Mouse islet immunostained for insulin

Mouse islet immunostained for glucagon

See also

• Human anatomy
• Pancreatic hormone

References

External links

• MeSH A03.734.414
• "Pancreas, human - H&E", Blue Histology - Accessory Digestive Glands, School of Anatomy and Human Biology, The University of Western Australia