Beta cell
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.[1] Constituting ~50–70% of cells in human islets, beta cells play a vital role in maintaining blood glucose levels.[2] Problems with beta cells can lead to disorders such as diabetes.[3]
Beta cell
Function[edit]
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.[4] Insulin facilitates the uptake of glucose by cells, allowing them to use it for energy or store it for future use.[5] Amylin helps regulate the rate at which glucose enters the bloodstream after a meal, slowing down the absorption of nutrients by inhibit gastric emptying.[6]
Insulin synthesis[edit]
Beta cells are the only site of insulin synthesis in mammals.[7] As glucose stimulates insulin secretion, it simultaneously increases proinsulin biosynthesis through translational control and enhanced gene transcription.[4][8]
The insulin gene is first transcribed into mRNA and translated into preproinsulin.[4] After translation, the preproinsulin precursor contains an N-terminal signal peptide that allows translocation into the rough endoplasmic reticulum (RER).[9] Inside the RER, the signal peptide is cleaved to form proinsulin.[9] Then, folding of proinsulin occurs forming three disulfide bonds.[9] Subsequent to protein folding, proinsulin is transported to the Golgi apparatus and enters immature insulin granules where proinsulin is cleaved to form insulin and C-peptide.[9] After maturation, these secretory vesicles hold insulin, C-peptide, and amylin until calcium triggers exocytosis of the granule contents.[4]
Through translational processing, insulin is encoded as a 110 amino acid precursor but is secreted as a 51 amino acid protein.[9]
Research[edit]
Experimental techniques[edit]
Many researchers around the world are investigating the pathogenesis of diabetes and beta-cell failure. Tools used to study beta-cell function are expanding rapidly with technology.
For instance, transcriptomics have allowed researchers to comprehensively analyze gene transcription in beta-cells to look for genes linked to diabetes.[2] A more common mechanism of analyzing cellular function is calcium imaging. Fluorescent dyes bind to calcium and allow in vitro imaging of calcium activity which correlates directly with insulin release.[2][33] 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[34] or alloxan,[35] 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.[36]
Type 1 diabetes[edit]
Research has shown that beta cells can be differentiated from human pancreas progenitor cells.[37] These differentiated beta cells, however, often lack much of the structure and markers that beta cells need to perform their necessary functions.[37] Examples of the anomalies that arise from beta cells differentiated from progenitor cells include a failure to react to environments with high glucose concentrations, an inability to produce necessary beta cell markers, and abnormal expression of glucagon along with insulin.[37]
In order to successfully re-create functional insulin producing beta cells, studies have shown that manipulating cell-signal pathways in early stem cell development will lead to those stem cells differentiating into viable beta cells.[37][38] Two key signal pathways have been shown to play a vital role in the differentiation of stem cells into beta cells: the BMP4 pathway and the kinase C.[38] Targeted manipulation of these two pathways has shown that it is possible to induce beta cell differentiation from stem cells.[38] These variations of artificial beta cells have shown greater levels of success in replicating the functionality of natural beta cells, although the replication has not been perfectly re-created yet.[38]
Studies have shown that it is possible to regenerate beta cells in vivo in some animal models.[39] 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.[37] While these studies have conclusive results in mice, beta cells in human subjects may not possess this same level of versatility. Investigation of beta cells following acute onset of Type 1 diabetes has shown little to no proliferation of newly synthesized beta cells, suggesting that human beta cells might not be as versatile as rat beta cells, but there is actually no comparison that can be made here because healthy (non-diabetic) rats were used to prove that beta cells can proliferate after intentional destruction of beta cells, while diseased (type-1 diabetic) humans were used in the study which was attempted to use as evidence against beta cells regenerating.[40]
It appears that much work has to be done in the field of regenerating beta cells.[38] 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[edit]
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.[2][4][9] Another topic of interest for beta-cell physiologists is the mechanism of insulin pulsatility which has been well investigated.[41][42] Many genome studies have been completed and are advancing the knowledge of beta-cell function exponentially.[43][44] Indeed, the area of beta-cell research is very active yet many mysteries remain.