Pancreatic islets

There are about 1 million islets distributed throughout the pancreas of a healthy adult human. While islets vary in size, the average diameter is about 0.2 mm.: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. • Alpha cells producing glucagon (20% of total islet cells) • Beta cells producing insulin and amylin (≈70%) • PP cells (gamma cells or F cells) producing pancreatic polypeptide ( 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 paracrine 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. Also inhibits the secretion of pancreatic polypeptide. 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). 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 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 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. 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 following three decades. 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. 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. Islet transplantation for type 1 diabetes () requires potent immunosuppression to prevent host rejection of donor islets. The islets are transplanted into a portal vein, which is then implanted in the liver. 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. Cryopreservation has shown promise to improve the supply chain of pancreatic islets for better transplantation outcomes. == Other Animals ==

Extensive comparative anatomy work has been done to study the evolution of pancreatic islets across representatives of all major groups of vertebrates and a number of different invertebrates. Islet organs are absent in any invertebrate and primitive chordates (tunicates and lancelets). During the evolution of vertebrates, the cell types secreting peptides related to insulin, somatostatin, glucagon, and PP moved from the brain to the gastrointestinal track mucosa (insulin first in tunicates, all four in lancelets), and then migrated out sequentially to form an islet structure (insulin and somatostatin first in jawless fish, followed by glucagon in jawed cartilaginous fish, few or no PP in lobe-finned bony fish, numerous PP in some ray-finned bony fish, ghrelin detected in catfish). In birds, other peptide-secreting cells such as IGF-1, PYY, and adrenomedullin have been localized in the islets. Notably, American anglerfish pancreas — unlike those of mammals — has islets that are rich in endocrine cells and mostly free of pancreatic exocrine tissue, making them ideal sources of endocrine cells for research. It eventually enabled the isolation of the cDNA for preproglucagon, which contained the sequence for glucagon and two other glucagon-like peptides (GLP-1 and GLP-2). == Research ==

Cannabinoid receptors are found widely expressed in islets of Langerhans, and several studies have investigated specific distribution and mechanisms of CB1 versus CB2 receptors in relation to pancreatic endocrine functions, where they play an important homeostatic role, as endocannabinoids modulate pancreatic β-cells function, proliferation, and survival, as well as insulin production, secretion, and resistance. ==Additional images==

Langerhanssche Insel.jpg|Pancreatic islets, the lighter tissue among the darker, acinar pancreatic tissue, hemalum-eosin 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 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. == See also ==