Editing Beta cell (section)

== Research ==
=== Experimental techniques ===
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.<ref name="Chen_2017" /> 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.<ref name="Chen_2017" /><ref>{{cite journal | vauthors = Whitticar NB, Strahler EW, Rajan P, Kaya S, Nunemaker CS | title = An Automated Perifusion System for Modifying Cell Culture Conditions over Time | journal = Biological Procedures Online | volume = 18 | issue = 1 | pages = 19 | date = 2016-11-21 | pmid = 27895534 | pmc = 5117600 | doi = 10.1186/s12575-016-0049-7 | doi-access = free }}</ref> 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]]<ref>{{cite journal | vauthors = Wang Z, Gleichmann H | title = GLUT2 in pancreatic islets: crucial target molecule in diabetes induced with multiple low doses of streptozotocin in mice | journal = Diabetes | volume = 47 | issue = 1 | pages = 50–56 | date = January 1998 | pmid = 9421374 | doi = 10.2337/diabetes.47.1.50 }}</ref> or [[alloxan]],<ref>{{cite journal | vauthors = Danilova IG, Sarapultsev PA, Medvedeva SU, Gette IF, Bulavintceva TS, Sarapultsev AP | title = Morphological restructuring of myocardium during the early phase of experimental diabetes mellitus | journal = Anatomical Record | volume = 298 | issue = 2 | pages = 396–407 | date = February 2015 | pmid = 25251897 | doi = 10.1002/ar.23052 | s2cid = 205412167 | doi-access = free | hdl = 10995/73117 | hdl-access = free }}</ref> 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.<ref>{{cite journal | vauthors = King AJ | title = The use of animal models in diabetes research | journal = British Journal of Pharmacology | volume = 166 | issue = 3 | pages = 877–894 | date = June 2012 | pmid = 22352879 | pmc = 3417415 | doi = 10.1111/j.1476-5381.2012.01911.x }}</ref>

=== Type 1 diabetes ===

Research has shown that beta cells can be differentiated from human pancreas progenitor cells.<ref name="Afelik_2017">{{cite journal | vauthors = Afelik S, Rovira M | title = Pancreatic β-cell regeneration: Facultative or dedicated progenitors? | journal = Molecular and Cellular Endocrinology | volume = 445 | pages = 85–94 | date = April 2017 | pmid = 27838399 | doi = 10.1016/j.mce.2016.11.008 | s2cid = 21795162 }}</ref> These differentiated beta cells, however, often lack much of the structure and markers that beta cells need to perform their necessary functions.<ref name="Afelik_2017" /> 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.<ref name="Afelik_2017" />

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.<ref name="Afelik_2017" /><ref name="Mahla_2016" /> 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.<ref name="Mahla_2016" /> Targeted manipulation of these two pathways has shown that it is possible to induce beta cell differentiation from stem cells.<ref name="Mahla_2016" /> 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.<ref name="Mahla_2016" />

Studies have shown that it is possible to regenerate beta cells ''in vivo'' in some animal models.<ref>{{cite journal | vauthors = Jeon K, Lim H, Kim JH, Thuan NV, Park SH, Lim YM, Choi HY, Lee ER, Kim JH, Lee MS, Cho SG | title = Differentiation and transplantation of functional pancreatic beta cells generated from induced pluripotent stem cells derived from a type 1 diabetes mouse model | journal = Stem Cells and Development | volume = 21 | issue = 14 | pages = 2642–2655 | date = September 2012 | pmid = 22512788 | pmc = 3438879 | doi = 10.1089/scd.2011.0665 }}</ref> 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.<ref name="Afelik_2017" /> 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.<ref>Lam, Carol & Jacobson, Daniel & Rankin, Matthew & Cox, Aaron & Kushner, Jake. (2017). β Cells Persist in T1D Pancreata Without Evidence of Ongoing β-Cell Turnover or Neogenesis. The Journal of clinical endocrinology and metabolism. 102. 10.1210/jc.2016-3806.</ref>

It appears that much work has to be done in the field of regenerating beta cells.<ref name="Mahla_2016">
{{cite journal | vauthors = Mahla RS | title = Stem Cells Applications in Regenerative Medicine and Disease Therapeutics | journal = International Journal of Cell Biology | volume = 2016 | issue = 7 | pages = 6940283 | year = 2016 | pmid = 27516776 | pmc = 4969512 | doi = 10.1155/2016/6940283 | doi-access = free }}</ref> 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.<ref name="Chen_2017" /><ref name="Boland_2017" /><ref name="Fu_2013" /> Another topic of interest for beta-cell physiologists is the mechanism of insulin pulsatility which has been well investigated.<ref>{{cite journal | vauthors = Nunemaker CS, Bertram R, Sherman A, Tsaneva-Atanasova K, Daniel CR, Satin LS | title = Glucose modulates [Ca2+]i oscillations in pancreatic islets via ionic and glycolytic mechanisms | journal = Biophysical Journal | volume = 91 | issue = 6 | pages = 2082–2096 | date = September 2006 | pmid = 16815907 | pmc = 1557567 | doi = 10.1529/biophysj.106.087296 | bibcode = 2006BpJ....91.2082N }}</ref><ref>{{cite journal | vauthors = Bertram R, Sherman A, Satin LS | title = Metabolic and electrical oscillations: partners in controlling pulsatile insulin secretion | journal = American Journal of Physiology. Endocrinology and Metabolism | volume = 293 | issue = 4 | pages = E890–E900 | date = October 2007 | pmid = 17666486 | doi = 10.1152/ajpendo.00359.2007 }}</ref> Many genome studies have been completed and are advancing the knowledge of beta-cell function exponentially.<ref>{{cite journal | vauthors = Muraro MJ, Dharmadhikari G, Grün D, Groen N, Dielen T, Jansen E, van Gurp L, Engelse MA, Carlotti F, de Koning EJ, van Oudenaarden A | title = A Single-Cell Transcriptome Atlas of the Human Pancreas | journal = Cell Systems | volume = 3 | issue = 4 | pages = 385–394.e3 | date = October 2016 | pmid = 27693023 | pmc = 5092539 | doi = 10.1016/j.cels.2016.09.002 }}</ref><ref>{{cite journal | vauthors = Segerstolpe Å, Palasantza A, Eliasson P, Andersson EM, Andréasson AC, Sun X, Picelli S, Sabirsh A, Clausen M, Bjursell MK, Smith DM, Kasper M, Ämmälä C, Sandberg R | title = Single-Cell Transcriptome Profiling of Human Pancreatic Islets in Health and Type 2 Diabetes | journal = Cell Metabolism | volume = 24 | issue = 4 | pages = 593–607 | date = October 2016 | pmid = 27667667 | pmc = 5069352 | doi = 10.1016/j.cmet.2016.08.020 }}</ref> Indeed, the area of beta-cell research is very active yet many mysteries remain.