Beta cell

The beta cells or insulin-secreting cells are one of the types of endocrine cells located in the islets of Langerhans of the pancreas. They synthesize, store, and secrete the hormone insulin that lowers blood glucose levels (glycemia).

Features

Beta cells are endocrine cells located in the pancreatic islets. They show the specific molecular and ultrastructural elements, which allow characterizing their insulin secretion capacity.

Microarchitecture

To identify insulin-secreting beta (β) cells, special staining methods such as Gomori staining or staining by immunohistochemistry or immunofluorescence are required.

File:Beta-cells of islets of Langerhans.jpg

Beta cells (β), cytoplasm is stained by immunohistochemical antibodies anti insulin. Optical microscope

In the pancreatic islet the proportion of β cells varies by species.
The three-dimensional location of β cells within the islet also differs between species.
The so-called β cells represent the majority of the endocrine cells of the islet. With H&E staining and Gomori staining they appear relatively small and blue in color.

Mouse whirl. Immunohistochemical: insulin cells (green), glucagon cells (red), collagen of the extracellular matrix (yellow).

The spatial architecture of endocrine cell types within the islet is important for its function, as intercellular contact and paracrine signaling between cells optimize hormone secretion.

Mouse/rat islets show typical core and mantle architecture with β cells in the center.
In human pancreatic islets β cells are interspersed with α, δ, G, cells. γ and ε.

The β cells show the shape of truncated pyramids that are grouped around the blood vessels of the islets. β cells have an average diameter of 10 micrometers (μm). The nucleus of the β cell is located near its base, in the vicinity of the arteriole. Insulin granules are enriched at the apex, next to the venule.

β are the predominant cell type in islets. An average islet of Langerhans contains a total of 1,000 to 3,000 cells, of which 50 to 80% are beta (β) cells. Estimates made suggest that a mouse pancreas could contain 1 × 10⁶ beta cells (1 milligram mg of beta cells) and a human pancreas contains 1 × 10⁹ beta cells (1 gram g of beta cells). The β they contain about 20 picograms (pg) of insulin per cell.

Ultrastructure

File:Celula beta granulos.png structure

Cell beta β with numerous dark center gallbladders. N= core. The continuous line marks the plasma membrane.

Beta cell. Yellow= Nucleus; Green= Golgi; Blue= mitochondria; Red= insulin granules. 3D reconstruction Electronic microscopy.

Insulin granules in a beta cell.
IG= immature; MG= mature.

Under electron microscope (EM) insulin-secreting cells (β cells) show average diameters of 10 micrometers (μm) with a length of ~17 μm.
Total surface area membrane of a β cell, was estimated to be ≈973 square micrometers (µm²).
The calculated volume of the β cell would be ≈1430 cubic micrometers (µm³) on average.

Core

The β cell nucleus is clear because the less compact DNA (euchromatin) predominates, containing the genes that are being actively and permanently transcribed (gene expression) by the cell.
The calculated volume of the mouse cell nucleus is between 110-160 cubic micrometers (µm³), which represents 14-16% of the total cell volume.

Golgi

The Golgi apparatus of the β cell is responsible for the modification and distribution of proteins (proinsulin) that have been synthesized in the endoplasmic reticulum and surrounds them with a membrane creating vesicles (called insulin granules). insulin) to secrete them out of the cell. The Golgi volume of the β cell is between 18-22 µm³ which is 0.90-2.20% of the cell volume.

Insulin granules

Insulinogenic granules of β cells are characterized by an irregularly spheroidal-shaped electron-dense center (electro-dense), and a pale-looking peripheral halo (mature granules (MG)). The contents separate from the limiting membrane after the fixation used for EM, appearing as a white periphery (electro-lucid) due to the empty space that is generated.
The size of insulin granules is around 300 nanometers (nm) and their average number has been estimated at ~10,000 in each beta cell.

immature “grises” granules (IG): contain proinsulin that is not yet fully processed, the dark dense core is absent.

coupled granules: is a fraction of granules that is very close to the cell membrane, represent a defined population and ready for exocytosis.

Apical membrane

Beta cells are known to possess abundant microvilli which determine the velvety appearance of their surface.

Synthesis, processing and packaging of insulin

Insulin Synthesis

Insulin is synthesized in the rough endoplasmic reticulum of the β cell in the form of a polypeptide called pre-proinsulin that is transformed into pro-insulin, which has the same hormonal activity although not the same. same magnitude as insulin. Proinsulin is modified in the Golgi apparatus, and the secretory vesicles that exit the complex contain the hormone insulin.

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Beta cell. Insulin granules are the dark black spots surrounded by a white area called halo. Rat beta cell. NASA image technology. Optical microscope.

The β cells make insulin in stages. The first stage is the production of proinsulin. Proinsulin is a molecule formed by a protein chain of 81 amino acids, which is a precursor of insulin. Beta cells of the pancreas process proinsulin into insulin by enzymatic removal of C-peptide, which is a 30-amino acid structure connecting the A and B chains (21 and 30 amino acids long, respectively).

Insulin is secreted in response to hyperglycemia and also by some peptide hormones such as glucagon, cholecystokinin-pancreozymin, and secretin. Its main actions are to stimulate glucose uptake in various types of cells, concomitantly lowering the blood glucose level, by stimulating the conversion of glucose into glycogen in hepatocytes and myocytes, whenever said level increases.

Proteome

20% of the total mRNA mass in beta cells is insulin mRNA, and the estimated total insulin content in the human pancreas is approximately 10 mg (1% of beta cell weight), which corresponds to 10 days of secretion by healthy people.

In type 1 diabetes, the immune system destroys Beta cells due to an autoimmune reaction that may involve both its Zinc transporter, ZnT8; to glutamate decarboxylase (GAD); to insulin itself or to other molecules. Without the beta cells, the pancreas cannot produce insulin, which causes an increase in glucose levels with the short- and long-term consequences of diabetes.

Insulin release

File:Celula beta granulos.png structure

Plasma membrane-coupled granules PM (fleets), soon for exocytosis.

In the insulin-secreting beta (β) cell, a population of granules are in contact with the plasma membrane. These coupled granules bind by fusion of the bilayer of the granules with the plasma membrane, releasing their insulin content by exocytosis.
The insulin released by the secretory vesicles of the β cells, is released directly into the interstitial space, from where it passes into the fenestrated capillaries of the islet and from there into the portal vein.
In an adult human, beta cells release between 30 and 70 Units of insulin per day depending on body weight.

Regulation of the beta cell

Insulin-secreting cells (β cells), in addition to glucose, are regulated by various levels of paracrine, endocrine, neuronal, and nutritional inputs that collectively determine their activity.
Insulin release is regulated by a complex network of many different signals that activate, potentiate or inhibit β cells. The main signal that triggers insulin secretion in β cells is glucose and has transmission that transforms from chemical signals to electrical signals and mechanical signals.

Cellular turnover of beta cells

Beta cell replication levels and beta cell apoptosis are balanced. The balance allows for the gradual replacement of the beta cell population which should be considered a slowly renewing tissue.
Beta cell mass is controlled by several mechanisms, including beta cell replication, neogenesis, hypertrophy, and survival.

Beta cell pathology

The pathology of the cells that secrete the hormone insulin is known as β cell failure .
The failure of β cells to respond to the increased demand for insulin, due to the progressive resistance of peripheral tissues to the hormone, is the hallmark of type 2 diabetes.
It is controversial whether β cell dysfunction is an early abnormality of type 2 diabetes, or occurs late in the natural history. It appears that beta cell function declines early in the disease process and declines progressively as glucose tolerance deteriorates.
At the onset of type 2 diabetes, there is a 50–80% reduction in total β cell mass.
In newly diagnosed patients with type 1 diabetes, an acute loss of 90% of β cells is found.

Beta cell transplantation

Replacing insulin-secreting cells has the potential to cure type 1 diabetes and possibly type 2 diabetes as well.
The transplant can be autologous or heterologous, either from multicellular islets or from isolated cells.

Islets

Pancreatic islet therapy is used in some patients with type 1 diabetes, they are obtained from donors (heterologous).

Insulated cells

Embryonic stem cells (ESC) are obtained from donor (heterologists).

Adult stem cells or adults induced to pluripotents (iPSC), are autologous.