Editing Beta cell (section)

==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.<ref>{{cite journal | vauthors = Sakran N, Graham Y, Pintar T, Yang W, Kassir R, Willigendael EM, Singhal R, Kooreman ZE, Ramnarain D, Mahawar K, Parmar C, Madhok B, Pouwels S | title = The many faces of diabetes. Is there a need for re-classification? A narrative review | journal = BMC Endocrine Disorders | volume = 22 | issue = 1 | pages = 9 | date = January 2022 | pmid = 34991585 | pmc = 8740476 | doi = 10.1186/s12902-021-00927-y | doi-access = free }}</ref> 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.<ref name="Fu_2013" /> The process of beta-cell destruction begins with insulitis activating antigen-presenting cells (APCs). APCs then trigger activation of CD4+ helper-T cells and chemokines/cytokines release. Then, the cytokines activate CD8+ cytotoxic–T cells which leads to beta-cell destruction.<ref>{{cite journal | vauthors = Tomita T | title = Apoptosis of pancreatic β-cells in Type 1 diabetes | journal = Bosnian Journal of Basic Medical Sciences | volume = 17 | issue = 3 | pages = 183–193 | date = August 2017 | pmid = 28368239 | pmc = 5581966 | doi = 10.17305/bjbms.2017.1961 }}</ref> 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.<ref>{{cite journal | vauthors = Eizirik DL, Mandrup-Poulsen T | title = A choice of death--the signal-transduction of immune-mediated beta-cell apoptosis | journal = Diabetologia | volume = 44 | issue = 12 | pages = 2115–2133 | date = December 2001 | pmid = 11793013 | doi = 10.1007/s001250100021 | doi-access = free }}</ref> The body destroys 70–80% of beta cells, leaving only 20–30% of functioning cells.<ref name="Chen_2017" /><ref>{{cite journal | vauthors = Butler AE, Galasso R, Meier JJ, Basu R, Rizza RA, Butler PC | title = Modestly increased beta cell apoptosis but no increased beta cell replication in recent-onset type 1 diabetic patients who died of diabetic ketoacidosis | journal = Diabetologia | volume = 50 | issue = 11 | pages = 2323–2331 | date = November 2007 | pmid = 17805509 | doi = 10.1007/s00125-007-0794-x | doi-access = free }}</ref> This can cause the patient to experience hyperglycemia, which leads to other adverse short-term and long-term conditions.<ref name="Ciechanowski_2003">{{cite journal | vauthors = Ciechanowski PS, Katon WJ, Russo JE, Hirsch IB | title = The relationship of depressive symptoms to symptom reporting, self-care and glucose control in diabetes | journal = General Hospital Psychiatry | volume = 25 | issue = 4 | pages = 246–252 | date = July–August 2003 | pmid = 12850656 | doi = 10.1016/s0163-8343(03)00055-0 }}</ref> The symptoms of diabetes can potentially be controlled with methods such as regular doses of insulin and sustaining a proper diet.<ref name="Ciechanowski_2003" /> However, these methods can be tedious and cumbersome to continuously perform on a daily basis.<ref name="Ciechanowski_2003" />

=== Type 2 diabetes ===
[[Type 2 diabetes]], also known as non insulin dependent diabetes and as chronic hyperglycemia, is caused primarily by genetics and the development of metabolic syndrome.<ref name="Chen_2017" /><ref name="Fu_2013" /> The beta cells can still secrete insulin but the body has developed a resistance and its response to insulin has declined.<ref name="Boland_2017" /> It is believed to be due to the decline of specific receptors on the surface of the [[liver]], [[Adipose tissue|adipose]], and [[muscle cells]] which lose their ability to respond to insulin that circulates in the blood.<ref>{{cite journal | vauthors =  | title = U.K. prospective diabetes study 16. Overview of 6 years' therapy of type II diabetes: a progressive disease. U.K. Prospective Diabetes Study Group | journal = Diabetes | volume = 44 | issue = 11 | pages = 1249–1258 | date = November 1995 | pmid = 7589820 | doi = 10.2337/diabetes.44.11.1249 }}</ref><ref>{{cite journal | vauthors = Rudenski AS, Matthews DR, Levy JC, Turner RC | title = Understanding "insulin resistance": both glucose resistance and insulin resistance are required to model human diabetes | journal = Metabolism | volume = 40 | issue = 9 | pages = 908–917 | date = September 1991 | pmid = 1895955 | doi = 10.1016/0026-0495(91)90065-5 }}</ref> In an effort to secrete enough insulin to overcome the increasing insulin resistance, the beta cells increase their function, size and number.<ref name="Boland_2017" /> Increased insulin secretion leads to hyperinsulinemia, but blood glucose levels remain within their normal range due to the decreased efficacy of insulin signaling.<ref name="Boland_2017" /> However, the beta cells can become overworked and exhausted from being overstimulated, leading to a 50% reduction in function along with a 40% decrease in beta-cell volume.<ref name="Fu_2013" /> At this point, not enough insulin can be produced and secreted to keep blood glucose levels within their normal range, causing overt type 2 diabetes.<ref name="Fu_2013" />

=== Insulinoma ===
[[Insulinoma]] is a rare tumor derived from the neoplasia of beta cells. Insulinomas are usually [[benign]], but may be medically significant and even life-threatening due to recurrent and prolonged attacks of [[hypoglycemia]].<ref>{{cite journal | vauthors = Yu R, Nissen NN, Hendifar A, Tang L, Song YL, Chen YJ, Fan X | title = A Clinicopathological Study of Malignant Insulinoma in a Contemporary Series | journal = Pancreas | volume = 46 | issue = 1 | pages = 48–56 | date = January 2017 | pmid = 27984486 | doi = 10.1097/MPA.0000000000000718 | s2cid = 3723691 }}</ref>

=== 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.<ref>{{cite journal | vauthors = Bolen S, Feldman L, Vassy J, Wilson L, Yeh HC, Marinopoulos S, Wiley C, Selvin E, Wilson R, Bass EB, Brancati FL | title = Systematic review: comparative effectiveness and safety of oral medications for type 2 diabetes mellitus | journal = Annals of Internal Medicine | volume = 147 | issue = 6 | pages = 386–399 | date = September 2007 | pmid = 17638715 | doi = 10.7326/0003-4819-147-6-200709180-00178 | doi-access = free }}</ref><ref name="Inzucchi_2012">{{cite journal | vauthors = Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, Peters AL, Tsapas A, Wender R, Matthews DR | title = Management of hyperglycaemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) | journal = Diabetologia | volume = 55 | issue = 6 | pages = 1577–1596 | date = June 2012 | pmid = 22526604 | doi = 10.1007/s00125-012-2534-0 | doi-access = free }}</ref> These drugs are known to cause hypoglycemia and can lead to beta-cell failure due to overstimulation.<ref name="Chen_2017" /> Second-generation versions of sulfonylureas are shorter acting and less likely to cause hypoglycemia.<ref name="Inzucchi_2012" />
* GLP-1 receptor agonists stimulate insulin secretion by simulating activation of the body's endogenous incretin system.<ref name="Inzucchi_2012" /> The incretin system acts as an insulin secretion amplifying pathway.<ref name="Inzucchi_2012" />
* DPP-4 inhibitors block DPP-4 activity which increases postprandial incretin hormone concentration, therefore increasing insulin secretion.<ref name="Inzucchi_2012" />