The islets of Langerhans are the regions of
the pancreas that contain its endocrine cells. Discovered in 1869 by German pathological
anatomist Paul Langerhans, the islets of Langerhans constitute approximately 1% to 2% of the mass
of the pancreas. Structure
There are about one million islets distributed throughout the pancreas of a healthy adult
human,:914 each of which measures about 0.2 mm in diameter.:914 Each 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.:914
The combined mass of the islets is 1 to 1.5 grams. Histology
Hormones produced in the islets of Langerhans are secreted directly into the blood flow
by five types of cells. In rat islets, endocrine cell subsets are distributed as follows:
Alpha cells producing glucagon Beta cells producing insulin and amylin
Delta cells producing somatostatin PP cells producing pancreatic polypeptide
Epsilon cells producing ghrelin 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 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.
Islets can influence each other through paracrine and autocrine communication, and beta cells
are coupled electrically to other beta cells. Function
The paracrine feedback system of the islets of Langerhans 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 receptors regulates 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. 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 islets of Langerhans contain beta cells,
which secrete insulin, and play a significant role in diabetes.
Transplantation Restoration of metabolic control via the transplantation
of islets of Langerhans is an appealing approach. This can be achieved by transplantation of
the pancreas as vascularized organ or of isolated pancreatic islets. Islet transplantation has
emerged as a viable option for the treatment of insulin requiring diabetes in the early
1970s with steady progress over the last three decades.
Islet 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.
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. Islet transplantation for type 1 diabetes
currently requires potent immunosuppression to prevent host rejection of donor islets.
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. Another potential source of beta cells may
be xenotransplantation. The most likely source for xenogeneic islets for transplantation
into human under evaluation is the pig pancreas. Interestingly, human and porcine insulin differ
only for one amino acid, and insulin extracted from porcine pancreata has been used for the
treatment of patients with diabetes before the development of recombinant human insulin
technology. Several studies in small and large animals models have shown that transplantation
of islet cells across species is possible. However, several problems need to be overcome
for porcine islet transplantation to become a viable clinical option. The immunogenicity
of xenogeneic tissues may be different from and even stronger than allogeneic tissues.
For instance, Galalpha1-3Galbeta1-4GlcNAc expressed on porcine cells represents a major
barrier to xenotransplantation being the target of preformed antibodies present in human blood.
Remarkable progress has been recorded in the development of genetically modified pigs lacking
or overexpressing molecules that may improve acceptance of transplanted tissues across
into humans. Pigs lacking alpha-Gal or overexpressing human decay accelerating factor, amongst others,
have been generated to study the impact on transplanted outcome in nonhuman primate models.
Another possible antigenic target is the Hanganutziu-Deichter antigen, a sialic acid found in pigs and not
humans, which may contribute to immunogenicity of porcine islets. Another limitation is the
risk for transmission of zoonotic infections from pigs to humans, particularly from porcine
endogenous retro-viruses. Amongst the approaches proposed to overcome islet xenorejection is
immunoisolation of the clusters using encapsulation techniques that may shield them from immune
attack. Studies in rodents and large animals have shown great promise that justify cautious
optimism for the near future. Nonrandomized, uncontrolled pilot clinical trials are ongoing
in subject with insulin-requiring diabetes to test the efficacy of encapsulation techniques
to protect xenogeneic islets in the absence of chronic anti-rejection drugs.
Gallery Hormones/islet architecture See also
Betatrophin Human anatomy
Pancreatic hormone Neuroendocrine tumor
References External links
“The Islets of Langerhans”, Karolinska Institutet, Sweden
“Islets” Islet Society
MeSH A03.734.414 “Pancreas, human – H&E”, Blue Histology
– Accessory Digestive Glands, School of Anatomy and Human Biology,