thumb|219x219px|Human pancreatic islet by immunostaining. Nuclei of cells are shown in blue (DAPI). Beta cells are shown in green (Insulin), Delta cells are shown in white (Somatostatin).

Beta cells (β-cells) are specialized endocrine cells located within the pancreatic islets of Langerhans responsible for the production and release of insulin and amylin. Constituting ~50–70% of cells in human islets, beta cells play a vital role in maintaining blood glucose levels. Problems with beta cells can lead to disorders such as diabetes.

Function

The function of beta cells is primarily centered around the synthesis and secretion of hormones, particularly insulin and amylin. Both hormones work to keep blood glucose levels within a narrow, healthy range by different mechanisms. Insulin facilitates the uptake of glucose by cells, allowing them to use it for energy or store it for future use. Amylin helps regulate the rate at which glucose enters the bloodstream after a meal, slowing down the absorption of nutrients by inhibiting gastric emptying.

Insulin synthesis

Beta cells are the only site of insulin synthesis in mammals. As glucose stimulates insulin secretion, it simultaneously increases proinsulin biosynthesis through translational control and enhanced gene transcription.

The insulin gene is first transcribed into mRNA and translated into preproinsulin. Inside the RER, the signal peptide is cleaved to form proinsulin. There are four key events to the triggering pathway of GSIS: GLUT dependent glucose uptake, glucose metabolism, K<sub>ATP</sub> channel closure, and the opening of voltage gated calcium channels causing insulin granule fusion and exocytosis.

Voltage-gated calcium channels and ATP-sensitive potassium ion channels (K<sub>ATP</sub> channels) are embedded in the plasma membrane of beta cells. Under non-glucose stimulated conditions, the K<sub>ATP</sub> channels are open and the voltage gated calcium channels are closed. Via the K<sub>ATP</sub> channels, potassium ions move out of the cell, down their concentration gradient, making the inside of the cell more negative with respect to the outside (as potassium ions carry a positive charge).

When the glucose concentration outside the cell is high, glucose molecules move into the cell by facilitated diffusion, down its concentration gradient through glucose transporters (GLUT). Rodent beta cells primarily express the GLUT2 isoform, whereas human beta cells, although also expressing GLUT2, mainly make use of GLUT1 and GLUT3 isoforms. Since beta cells use glucokinase to catalyze the first step of glycolysis, metabolism only occurs around physiological blood glucose levels and above.

The K<sub>ATP</sub> channels close when the ATP to ADP ratio rises. The venous blood then eventually empties into the hepatic portal vein.

Other hormones secreted

  • C-peptide, which is secreted into the bloodstream in equimolar quantities to insulin. It helps to prevent neuropathy and other vascular deterioration related symptoms of diabetes mellitus. A practitioner would measure the levels of C-peptide to obtain an estimate for the viable beta cell mass.
  • Amylin, also known as islet amyloid polypeptide (IAPP). The function of amylin is to slow the rate of glucose entering the bloodstream. Amylin can be described as a synergistic partner to insulin, where insulin regulates long term food intake and amylin regulates short term food intake.

Clinical significance

Beta cells have significant clinical relevance as their proper function is essential for glucose regulation, and dysfunction is a key factor in the development and progression of diabetes and its associated complications. Here are some key clinical significances of beta cells:

Type 1 diabetes

Type 1 diabetes mellitus, also known as insulin-dependent diabetes, is believed to be caused by an auto-immune mediated destruction of the insulin-producing beta cells in the body. The destruction of these cells reduces the body's ability to respond to glucose levels in the body, therefore making it nearly impossible to properly regulate glucose and glucagon levels in the bloodstream. The body destroys 70–80% of beta cells, leaving only 20–30% of functioning cells. This can cause the patient to experience hyperglycemia, which leads to other adverse short-term and long-term conditions. The symptoms of diabetes can potentially be controlled with methods such as regular doses of insulin and sustaining a proper diet. In an effort to secrete enough insulin to overcome the increasing insulin resistance, the beta cells increase their function, size and number.

Medications

Many drugs to combat diabetes are aimed at modifying the function of the beta cell.

  • Sulfonylureas are insulin secretagogues that act by closing the ATP-sensitive potassium channels, thereby causing insulin release. These drugs are known to cause hypoglycemia and can lead to beta-cell failure due to overstimulation. Concerning calcium imaging, fluorescent dyes bind to calcium and allow in vitro imaging of calcium activity which correlates directly with insulin release. A final tool used in beta-cell research are in vivo experiments. Diabetes mellitus can be experimentally induced in vivo for research purposes by streptozotocin or alloxan, which are specifically toxic to beta cells. Mouse and rat models of diabetes also exist including ob/ob and db/db mice which are a type 2 diabetes model, and non-obese diabetic mice (NOD) which are a model for type 1 diabetes.

Type 1 diabetes

Research has shown that beta cells can be differentiated from human pancreas progenitor cells. These differentiated beta cells, however, often lack much of the structure and markers that beta cells need to perform their necessary functions. Research in mice has shown that beta cells can often regenerate to the original quantity number after the beta cells have undergone some sort of stress test, such as the intentional destruction of the beta cells in the mice subject or once the auto-immune response has concluded.

It appears that much work has to be done in the field of regenerating beta cells. Just as in the discovery of creating insulin through the use of recombinant DNA, the ability to artificially create stem cells that would differentiate into beta cells would prove to be an invaluable resource to patients with Type 1 diabetes. An unlimited amount of beta cells produced artificially could potentially provide therapy to many of the patients who are affected by Type 1 diabetes.

Type 2 diabetes

Research focused on non insulin dependent diabetes encompasses many areas of interest. Degeneration of the beta cell as diabetes progresses has been a broadly reviewed topic. Many genome studies have been completed and are advancing the knowledge of beta-cell function exponentially. Indeed, the area of beta-cell research is very active yet many mysteries remain.

See also

  • Gastric inhibitory polypeptide receptor
  • List of terms associated with diabetes
  • Guangxitoxin
  • Alpha cell
  • Pancreatic development
  • Islets of Langerhans
  • List of distinct cell types in the adult human body
  • Pancreatic beta cell function

References