The pancreatic islets or islets of Langerhans are the regions of the

pancreas The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e. it has both an en ...

that contain its endocrine (hormone-producing) cells, discovered in 1869 by

German German(s) may refer to: * Germany (of or related to) ** Germania (historical use) * Germans, citizens of Germany, people of German ancestry, or native speakers of the German language ** For citizens of Germany, see also German nationality law **Ge ...

pathological anatomist

Paul Langerhans Paul Langerhans (25 July 1847 – 20 July 1888) was a German pathologist, physiologist and biologist, credited with the discovery of the cells that secrete insulin, named after him as the islets of Langerhans. Eponymous terms * Islets of Langerh ...

. The pancreatic islets constitute 1–2% 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 Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, u ...

Structure

There are about 1 million islets distributed throughout the pancreas of a healthy adult human, each of which measures an average of about 0.2 mm in diameter.^:928 Each islet 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.^:928

Microanatomy

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 types are distributed as follows: * Alpha cells producing glucagon (20% of total islet cells) *

Beta cell Beta cells (β-cells) are a type of cell found in pancreatic islets that synthesize and secrete insulin and amylin. Beta cells make up 50–70% of the cells in human islets. In patients with Type 1 diabetes, beta-cell mass and function are di ...

s producing insulin and

amylin Amylin, or islet amyloid polypeptide (IAPP), is a 37-residue peptide hormone. It is co-secreted with insulin from the pancreatic β-cells in the ratio of approximately 100:1 (insulin:amylin). Amylin plays a role in glycemic regulation by sl ...

(≈70%) *

Delta cell Delta cells (δ-cells or D cells) are somatostatin-producing cells. They can be found in the stomach, intestine and the pancreatic islets. Delta cells comprise ca 5% of the cells in the islets but may interact with many more islet cells than sug ...

s producing somatostatin (<10%) * Epsilon cells producing

ghrelin Ghrelin (; or lenomorelin, INN) is a hormone produced by enteroendocrine cells of the gastrointestinal tract, especially the stomach, and is often called a "hunger hormone" because it increases the drive to eat. Blood levels of ghrelin are hi ...

(<1%) *

PP cell Pancreatic polypeptide cells (PP cells), or formerly as gamma cells (γ-cells), or F cells, are cells in the pancreatic islets (Islets of Langerhans) of the pancreas. Their main role is to help synthesize and regulate the release of pancreatic pol ...

s (gamma cells or F cells) producing

pancreatic polypeptide Pancreatic polypeptide (PP) is a polypeptide secreted by PP cells in the endocrine pancreas. It regulates pancreatic secretion activities, and also impacts liver glycogen storage and gastrointestinal secretion. Its secretion may be impacted by ...

(<5%) It has been recognized that the

cytoarchitecture Cytoarchitecture ( Greek '' κύτος''= "cell" + '' ἀρχιτεκτονική''= "architecture"), also known as cytoarchitectonics, is the study of the cellular composition of the central nervous system's tissues under the microscope. Cytoarc ...

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. The proportion of beta cells in islets varies depending on the species, in humans it is about 40–50%. In addition to endocrine cells, there are stromal cells (fibroblasts), vascular cells (endothelial cells, pericytes), immune cells (granulocytes, lymphocytes, macrophages, dendritic cells) and neural cells. A large amount of blood flows through the islets, 5–6 mL/min per 1 g of islet. It is up to 15 times more than in exocrine tissue of the pancreas. Islets can influence each other through

paracrine Paracrine signaling is a form of cell signaling, a type of cellular communication in which a cell produces a signal to induce changes in nearby cells, altering the behaviour of those cells. Signaling molecules known as paracrine factors diffuse over ...

and

autocrine Autocrine signaling is a form of cell signaling in which a cell secretes a hormone or chemical messenger (called the autocrine agent) that binds to autocrine receptors on that same cell, leading to changes in the cell. This can be contrasted with p ...

communication, and beta cells are coupled electrically to six to seven other beta cells, but not to other cell types. Human pancreatic islet.jpg, A pancreatic islet, stained. Alfa-cells of islets of Langerhans.jpg, A pancreatic islet, showing alpha cells Beta-cells of islets of Langerhans.jpg, A pancreatic islet, showing beta cells.

Function

The

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 receptor G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related p ...

s (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). File:PancreaticPolypeptide.jpg , Mouse islet immunostained for pancreatic polypeptide File:InsulinIHC.jpg , Mouse islet immunostained for insulin File:Glucagon.jpg , Mouse islet immunostained for glucagon

Electrical activity

Electrical activity of pancreatic islets has been studied using

patch clamp The patch clamp technique is a laboratory technique in electrophysiology used to study ionic currents in individual isolated living cells, tissue sections, or patches of cell membrane. The technique is especially useful in the study of excita ...

techniques. It has turned out that the behavior of cells in intact islets differs significantly from the behavior of dispersed cells.

Clinical significance

Diabetes

The

beta cell Beta cells (β-cells) are a type of cell found in pancreatic islets that synthesize and secrete insulin and amylin. Beta cells make up 50–70% of the cells in human islets. In patients with Type 1 diabetes, beta-cell mass and function are di ...

s of the pancreatic islets secrete insulin, and so play a significant role in

diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...

. It is thought that they are destroyed by immune assaults. 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 transplantation, 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 following 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 Brittle diabetes, unstable type 1 diabetes. People with high body mass index (BMI) are unsuitable pancreatic donors due to greater technical complications during transplantation. However, it is possible to isolate a larger number of islets because of their larger pancreas, and therefore they are more suitable donors of islets. Islet transplantation only involves the transfer of tissue consisting of beta cells that are necessary as a treatment of this disease. It thus represents an advantage over whole pancreas transplantation, which is more technically demanding and poses a risk of, for example, pancreatitis leading to organ loss. Another advantage is that patients do not require general anesthesia. Islet transplantation for type 1 diabetes currently requires potent immunosuppression to prevent host Transplant rejection, rejection of donor islets. The islets are transplanted into a portal vein, which is then implanted in the liver. There is a risk of portal venous branch thrombosis and the low value of islet survival a few minutes after transplantation, because the vascular density at this site is after the surgery several months lower than in endogenous islets. Thus, neovascularization is key to islet survival, that is supported, for example, by VEGF produced by islets and vascular endothelial cells. However, intraportal transplantation has some other shortcomings, and so other alternative sites that would provide better microenvironment for islets implantation are being examined. Islet transplant research also focuses on islet encapsulation, CNI-free (calcineurin-inhibitor) immunosuppression, biomarkers of islet damage or islet donor shortage. 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. Cyopreservation has shown promise to improve the supply chain of pancreatic islets for better transplantation outcomes. Zhan, L., Rao, J.S., Sethia, N. et al. Pancreatic islet cryopreservation by vitrification achieves high viability, function, recovery and clinical scalability for transplantation. Nat Med (2022). https://doi.org/10.1038/s41591-022-01718-1

Additional images

Langerhanssche Insel.jpg, Pancreatic islets, the lighter tissue among the darker, acinar pancreatic tissue, hemalum-eosin Staining, stain. File:Gray1105.png , Illustration of dog pancreas. 250x. File:Suckale08 fig2 islet structure.jpg , Structural differences between rat islets (top) and humans islets (bottom) as well as the Anatomical terms of location, ventral part (left) and the dorsal part (right) of the

. Different cell types are colour-coded. Rodent islets, unlike the human ones, show the characteristic insulin core.

References

External links

Pancreas
at the Human Protein Atlas {{DEFAULTSORT:Islets Of Langerhans Pancreas anatomy