Pancreatic Pathology Online

Normal Islets of Langerhans in the Pancreas

Dr Sampurna Roy MD              July 2016

 

Islets of Langerhans, which form the endocrine portion of the pancreas, are scattered throughout the organ and consist of richly vascularized globular masses of cells, which in the human pancreas are estimated to total from 200,000 to 2 million cells.

Islet cells in the pancreas

 

Six distinct cell types have been identified and correlated with hormone synthesis and storage.

Alpha cells, which contain glucagons, and beta cells, in which insulin is localized, have been best characterized.

The two types of delta cells, D and D1 (which secrete somatostatin and vasoactive intestinal polypeptide, respectively), and pancreatic polypeptide-secreting cells (PP cells - originally termed F cells) have been less well studied.

The enterochromaffin cells, which secrete the vasoactive amine serotonin (5-hydroxytryptamine), are a minor component of the istet cell population and are  demonstrable by their capacity for staining with potassium dichromate.

The cellular composition of islets varies in the different anatomic subdivisions as follows:  In the head the ratios of the component cells are beta > polypeptide-secreting  >delta  >alpha as contrasted with the body and tail, where the ratios are beta >alpha >delta >polypeptide-secreting.

Alpha cells are localized in the outer rim of the islets and constitute 15% to 20% of the total islet cell population.

 

In the alpha cells, glucagons, like insulin and other hormones, is synthesized as a prohormone, proglucagon, with a molecular of 19,000 daltons.

Before export the prohormone is cleaved to active  hormone, a 3500-dalton product.

Glucagon glycogenolysis and gluconeogenesis, thereby raising the blood glucose level.

Its secretion is stimulated by hypoglycemia, by the ingestion of a low-carbohydrate-high-protein meal, and by an intravenous infusion of amino acids.

By virtue of these responses by alpha cells,  glucagons, together with insulin serves to maintain fuel homeostasis.

At least two precursor peptides of proglucagon apparently constitute separate regions of the molecule.

These are called glicentins 1 and 2 and have been localized to the secretory granules in alpha cells.

Radioimmunoassay of glucagons in serum reveals several species, of which only the 3500-dalton variety appears to be biologically active.

Larger species, weighing 9000 daltons and 16,000 daltons, respectively, represent forms of the incompletely cleaved prohormone.

It is noteworthy that in patients with a rare condition called familial hyperglucagonemia, in whom the level of serum glucagon may be 10 times normal, 85% of the hormone consists of molecular forms higher than 9000 daltons.

Beta cells comprise the largest population, 60% to 70%, of cells in islets.

They are distributed throughout the islet when visualized by their affinity for certain stains, such as aldehude fuchsin or pseudoisoocyanin, or by specific antibody to insulin.

By electron microscopy the insulin is resolved into characteristic polygonal and rhomboidal crystals enclosed in secretory vesicles.

The synthesis and secretion pathway for insulin can  be considered as a general model for the other islet cell types.

Insulin is synthesized in the rough endoplasmic reticulum  of beta cells as a single chain precursor molecule, termed proinsulin, with a molecular weight of about 9000 daltons.

This molecule is transferred by an ATP-dependent process to Golgi membrane system, where it is packaged into smooth-surfaced microvesicles, and continuing in the secretory granules, Zn2+ is added  to the proinsulin molecule, after which it is progressively cleaved by membrane-bound proteases into equimolar amounts of insulin and the peptide that connects the A and B chains   of insulin (C-peptide).

The mature secretory granules, guided by the microtubules, migrate centripetally in the cytoplasm until they fuse with the plasma membrane and are extruded into the extracellular space, a process  termed exocytosis.

The final release involves an influx of Ca2+ ions into the cell.

As is true for a large number of other intracellular processes, cAMP participates in the insulin secretory process.

However, the major obligatory stimulus for insulin secretion is the binding of glucose to glucose receptors on surface of the beta cell.

Delta cells are fewer in number and slightly larger  than alpha cells.

Like alpha cells, delta cells tend to be localized at the periphery of islets.

They are situated between the alpha and the beta cells so that the three cell types are often contiguous.

Delta cells secrete somatostatin, a 1600-dalton  peptide identical to that discovered earlier in the hypothalamus that inhibits the pituitary release of growth hormone.

Somatostatin synthesized in the islets inhibits secretion by alpha and beta cells and one type(D1) of delta cell, acinar cells of the exocrine pancreas, and certain hormone-secreting cells in the gastrointestinal tract.

Coupled with the topographical cell-cell relations  noted earlier, these hormonal interactions suggest  that somatostatin plays a regulatory role in alpha and beta cell secretion, which is reflected in the high stability of glucose homeostasis.

D1 cells are smaller than the other islet cell types and are rare in the islets of normal human pancreas.

They synthesize a 3800-dalton peptide termed vasoactive intestinal polypeptide, a molecule that has also been localized in ganglion cells and nerve fibers of the pancreas, gut, and brain.

Vasoactive intestinal polypeptide induces glycogenolysis  and hyperglycemia, as does glucagons, and in addition regulates the tone, motility, and ion and water secretion by epithelial cells of the gastrointestinal tract.

The latter function is mediated by its ability to activate adenyl cyclase, thus leading to the production of cAMP.

Pancreatic polypeptide-producing cells are located primarily in the islets of the head of the pancreas and synthesize a 4300-dalton polypeptide, which appears to have variable and opposed functions.

These include stimulation of the secretion of enzymes from the gastric mucosa and inhibition of a variety of functions, such as smooth muscle contraction in the intestine and gallbladder, production of gastric acid, and secretion by the exocrine pancreas and biliary system.

Enterochromaffin cells, identified by their capacity for reducing ammoniacal silver and for staining by potassium dichromate, are rare components of the islet cell population in the head of the pancreas.

They synthesize serotonin, a vasoactive amine that causes vasodilatation and increased permeability of the venular capillaries, and the 2700-dalton peptide motilin, which stimulates motility of gastric smooth muscle, and increased the tone of the sphincter at the gastroesophageal junction.

Visit: Pancreatic Pathology Online ; Anatomy of Normal Pancreas  ; The Apud Concept.

 

Further reading:

The endocrine role between β cells and intra-islet endothelial cells [Review].

GPR120 (FFAR4) is preferentially expressed in pancreatic delta cells and regulates somatostatin secretion from murine islets of Langerhans.

Long-term culture and functionality of pancreatic islets monitored using microelectrode arrays.

Immunohistochemical study of α- and β-cell distribution in human pancreatic Langerhans islets of various types.

Protein-mediated interactions of pancreatic islet cells.

Transplantation of human islets without immunosuppression.

How to make a functional β-cell.

 

 

 

Dr Sampurna Roy  MD

Consultant  Histopathologist (Kolkata - India)


 

 

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