Editing Beta cell

{{short description|Type of cell found in pancreatic islets}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox cell
| Name        = Beta cell
| Latin       = endocrinocytus B; insulinocytus
| Image       =
| Caption     = The photo above shows a [[mouse]] [[pancreatic islet]] as seen by [[light microscopy]]. Beta cells can be recognised by the green [[insulin]] staining. [[Glucagon]] is labelled in red and the [[cell nucleus|nuclei]] in blue.
| Image2      =
| Caption2    = A '''pancreatic islet''' in a [[pig]]. The left image is a brightfield image created using [[hematoxylin]] stain; nuclei are dark circles and the [[acinar]] pancreatic tissue is darker than the islet tissue. The right image is the same section stained by immunofluorescence against insulin, indicating beta cells.
| Precursor   =
| System      =
| Location = [[Pancreatic islet]]
| Function = [[Insulin]] secretion
}}

[[File:Human Pancreatic Islet.tif|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 system|endocrine]] [[Cell (biology)|cells]] located within the [[pancreatic islets]] of Langerhans responsible for the production and release of [[insulin]] and [[amylin]].<ref>{{cite journal | vauthors = Dolenšek J, Rupnik MS, Stožer A | title = Structural similarities and differences between the human and the mouse pancreas | journal = Islets | volume = 7 | issue = 1 | pages = e1024405 | date = 2015-01-02 | pmid = 26030186 | doi = 10.1080/19382014.2015.1024405 | s2cid = 17908732 | doi-access = free | pmc = 4589993 }}</ref> Constituting ~50–70% of cells in human islets, beta cells play a vital role in maintaining blood [[glucose]] levels.<ref name="Chen_2017">{{cite journal | vauthors = Chen C, Cohrs CM, Stertmann J, Bozsak R, Speier S | title = Human beta cell mass and function in diabetes: Recent advances in knowledge and technologies to understand disease pathogenesis | journal = Molecular Metabolism | volume = 6 | issue = 9 | pages = 943–957 | date = September 2017 | pmid = 28951820 | pmc = 5605733 | doi = 10.1016/j.molmet.2017.06.019 }}</ref> Problems with beta cells can lead to disorders such as [[diabetes]].<ref>{{cite journal | vauthors = Ashcroft FM, Rorsman P | title = Diabetes mellitus and the β cell: the last ten years | journal = Cell | volume = 148 | issue = 6 | pages = 1160–1171 | date = March 2012 | pmid = 22424227 | pmc = 5890906 | doi = 10.1016/j.cell.2012.02.010 }}</ref>

== Function ==
The function of beta cells is primarily centered around the synthesis and secretion of [[hormone]]s, particularly insulin and amylin. Both hormones work to keep blood glucose levels within a narrow, healthy range by different mechanisms.<ref name="Boland_2017">{{cite journal | vauthors = Boland BB, Rhodes CJ, Grimsby JS | title = The dynamic plasticity of insulin production in β-cells | journal = Molecular Metabolism | volume = 6 | issue = 9 | pages = 958–973 | date = September 2017 | pmid = 28951821 | pmc = 5605729 | doi = 10.1016/j.molmet.2017.04.010 }}</ref> Insulin facilitates the uptake of glucose by cells, allowing them to use it for energy or store it for future use.<ref>{{cite journal | vauthors = Wilcox G | title = Insulin and insulin resistance | journal = The Clinical Biochemist. Reviews | volume = 26 | issue = 2 | pages = 19–39 | date = May 2005 | pmid = 16278749 | pmc = 1204764 }}</ref> Amylin helps regulate the rate at which glucose enters the bloodstream after a meal, slowing down the absorption of nutrients by inhibit gastric emptying.<ref>{{cite journal | vauthors = Westermark P, Andersson A, Westermark GT | title = Islet amyloid polypeptide, islet amyloid, and diabetes mellitus | journal = Physiological Reviews | volume = 91 | issue = 3 | pages = 795–826 | date = July 2011 | pmid = 21742788 | doi = 10.1152/physrev.00042.2009 }}</ref>

== Insulin synthesis ==
Beta cells are the only site of insulin synthesis in mammals.<ref>{{cite journal | vauthors = Boland BB, Brown C, Alarcon C, Demozay D, Grimsby JS, Rhodes CJ | title = β-Cell Control of Insulin Production During Starvation-Refeeding in Male Rats | journal = Endocrinology | volume = 159 | issue = 2 | pages = 895–906 | date = February 2018 | pmid = 29244064 | pmc = 5776497 | doi = 10.1210/en.2017-03120 }}</ref> As glucose stimulates insulin secretion, it simultaneously increases proinsulin biosynthesis through translational control and enhanced gene transcription.<ref name="Boland_2017" /><ref>{{cite journal | vauthors = Andrali SS, Sampley ML, Vanderford NL, Ozcan S | title = Glucose regulation of insulin gene expression in pancreatic beta-cells | journal = The Biochemical Journal | volume = 415 | issue = 1 | pages = 1–10 | date = October 2008 | pmid = 18778246 | doi = 10.1042/BJ20081029 }}</ref>

The [[Insulin|insulin gene]] is first transcribed into mRNA and translated into preproinsulin.<ref name="Boland_2017" /> After translation, the preproinsulin precursor contains an N-terminal signal peptide that allows translocation into the [[Endoplasmic reticulum|rough endoplasmic reticulum]] (RER).<ref name="Fu_2013">{{cite journal | vauthors = Fu Z, Gilbert ER, Liu D | title = Regulation of insulin synthesis and secretion and pancreatic Beta-cell dysfunction in diabetes | journal = Current Diabetes Reviews | volume = 9 | issue = 1 | pages = 25–53 | date = January 2013 | pmid = 22974359 | pmc = 3934755 | doi = 10.2174/157339913804143225 }}</ref> Inside the RER, the signal peptide is cleaved to form proinsulin.<ref name="Fu_2013" /> Then, folding of proinsulin occurs forming three disulfide bonds.<ref name="Fu_2013" /> 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]].<ref name="Fu_2013" /> After maturation, these secretory vesicles hold insulin, C-peptide, and amylin until calcium triggers [[exocytosis]] of the granule contents.<ref name="Boland_2017" />

Through translational processing, insulin is encoded as a 110 amino acid precursor but is secreted as a 51 amino acid protein.<ref name="Fu_2013" />

== Insulin secretion ==
[[File:Insulin secretion.png|alt=A diagram of the Consensus Model of glucose-stimulated insulin secretion|thumb|262x262px|The triggering pathway of glucose-stimulated insulin secretion]]
In beta cells, insulin release is stimulated primarily by glucose present in the blood.<ref name="Boland_2017"/> As circulating glucose levels rise, such as after ingesting a meal, insulin is secreted in a dose-dependent fashion.<ref name="Boland_2017" /> This system of release is commonly referred to as glucose-stimulated insulin secretion (GSIS).<ref>{{cite journal | vauthors = Komatsu M, Takei M, Ishii H, Sato Y | title = Glucose-stimulated insulin secretion: A newer perspective | journal = Journal of Diabetes Investigation | volume = 4 | issue = 6 | pages = 511–516 | date = November 2013 | pmid = 24843702 | pmc = 4020243 | doi = 10.1111/jdi.12094 }}</ref> There are four key events to the triggering pathway of GSIS: [[Glucose transporter|GLUT]] dependent glucose uptake, glucose metabolism, [[ATP-sensitive potassium channel|K<sub>ATP</sub> channel]] closure, and the opening of voltage gated calcium channels causing insulin granule fusion and exocytosis.<ref name="Kalwat_2017">{{cite journal | vauthors = Kalwat MA, Cobb MH | title = Mechanisms of the amplifying pathway of insulin secretion in the β cell | journal = Pharmacology & Therapeutics | volume = 179 | pages = 17–30 | date = November 2017 | pmid = 28527919 | pmc = 7269041 | doi = 10.1016/j.pharmthera.2017.05.003 }}</ref><ref name="Ramadan_2011">{{cite journal | vauthors = Ramadan JW, Steiner SR, O'Neill CM, Nunemaker CS | title = The central role of calcium in the effects of cytokines on beta-cell function: implications for type 1 and type 2 diabetes | journal = Cell Calcium | volume = 50 | issue = 6 | pages = 481–490 | date = December 2011 | pmid = 21944825 | pmc = 3223281 | doi = 10.1016/j.ceca.2011.08.005 }}</ref>

[[Voltage dependent calcium channel|Voltage-gated calcium channels]] and [[ATP sensitive potassium ion channel|ATP-sensitive potassium ion channels]] (K<sub>ATP</sub> channels) are embedded in the plasma membrane of beta cells.<ref name="Ramadan_2011" /><ref name="Ashcroft_1990">{{cite journal | vauthors = Ashcroft FM, Rorsman P | title = ATP-sensitive K+ channels: a link between B-cell metabolism and insulin secretion | journal = Biochemical Society Transactions | volume = 18 | issue = 1 | pages = 109–111 | date = February 1990 | pmid = 2185070 | doi = 10.1042/bst0180109 }}</ref> Under non-glucose stimulated conditions, the K<sub>ATP</sub> channels are open and the voltage gated calcium channels are closed.<ref name="Boland_2017" /><ref name=":0">{{cite journal | vauthors = Ashcroft FM, Rorsman P | title = K(ATP) channels and islet hormone secretion: new insights and controversies | journal = Nature Reviews. Endocrinology | volume = 9 | issue = 11 | pages = 660–669 | date = November 2013 | pmid = 24042324 | doi = 10.1038/nrendo.2013.166 | pmc = 5890885 }}</ref> 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).<ref name="Boland_2017" /> At rest, this creates a [[potential difference]] across the cell surface membrane of -70mV.<ref name="MacDonald_2005">{{cite journal | vauthors = MacDonald PE, Joseph JW, Rorsman P | title = Glucose-sensing mechanisms in pancreatic beta-cells | journal = Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences | volume = 360 | issue = 1464 | pages = 2211–2225 | date = December 2005 | pmid = 16321791 | pmc = 1569593 | doi = 10.1098/rstb.2005.1762 }}</ref>

When the glucose concentration outside the cell is high, glucose molecules move into the cell by [[facilitated diffusion]], down its concentration gradient through [[glucose transporter]]s (GLUT).<ref>{{cite journal | vauthors = De Vos A, Heimberg H, Quartier E, Huypens P, Bouwens L, Pipeleers D, Schuit F | title = Human and rat beta cells differ in glucose transporter but not in glucokinase gene expression | journal = The Journal of Clinical Investigation | volume = 96 | issue = 5 | pages = 2489–2495 | date = November 1995 | pmid = 7593639 | pmc = 185903 | doi = 10.1172/JCI118308 }}</ref> Rodent beta cells primarily express the [[GLUT2]] isoform, whereas human beta cells, although also expressing GLUT2, mainly make use of [[GLUT1]] and [[GLUT3]] isoforms.<ref>{{cite journal | vauthors = Berger C, Zdzieblo D | title = Glucose transporters in pancreatic islets | journal = Pflugers Archiv | volume = 472 | issue = 9 | pages = 1249–1272 | date = September 2020 | pmid = 32394191 | pmc = 7462922 | doi = 10.1007/s00424-020-02383-4 }}</ref><ref>{{cite journal | vauthors = Rorsman P, Ashcroft FM | title = Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men | journal = Physiological Reviews | volume = 98 | issue = 1 | pages = 117–214 | date = January 2018 | pmid = 29212789 | doi = 10.1152/phy }}</ref> Since beta cells use [[glucokinase]] to catalyze the first step of [[glycolysis]], metabolism only occurs around physiological [[blood glucose]] levels and above.<ref name="Boland_2017" /> Metabolism of glucose produces [[Adenosine triphosphate|ATP]], which increases the ATP to [[Adenosine diphosphate|ADP]] ratio.<ref name="JCI2015">{{cite journal | vauthors = Santulli G, Pagano G, Sardu C, Xie W, Reiken S, D'Ascia SL, Cannone M, Marziliano N, Trimarco B, Guise TA, Lacampagne A, Marks AR | title = Calcium release channel RyR2 regulates insulin release and glucose homeostasis | journal = The Journal of Clinical Investigation | volume = 125 | issue = 5 | pages = 1968–1978 | date = May 2015 | pmid = 25844899 | pmc = 4463204 | doi = 10.1172/JCI79273 }}</ref>

The K<sub>ATP</sub> channels close when the ATP to ADP ratio rises.<ref name="Ashcroft_1990" /> The closure of the K<sub>ATP</sub> channels causes the outward potassium ion current to diminish, leading to inward currents of potassium ions dominating.<ref name=":0" /> As a result, the potential difference across the membrane becomes more positive (as potassium ions accumulate inside the cell).<ref name="MacDonald_2005" /> This change in potential difference opens the [[voltage-gated calcium channels]], which allows calcium ions from outside the cell to move into the cell down their concentration gradient.<ref name="MacDonald_2005" /> When the calcium ions enter the cell, they cause [[vesicle (biology)|vesicles]] containing insulin to move to, and fuse with, the cell surface membrane, releasing insulin by [[exocytosis]] into the pancreatic capillaries.<ref>{{cite journal | vauthors = Lang V, Light PE | title = The molecular mechanisms and pharmacotherapy of ATP-sensitive potassium channel gene mutations underlying neonatal diabetes | journal = Pharmacogenomics and Personalized Medicine | volume = 3 | pages = 145–161 | year = 2010 | pmid = 23226049 | pmc = 3513215 | doi = 10.2147/PGPM.S6969 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Edgerton DS, Kraft G, Smith M, Farmer B, Williams PE, Coate KC, Printz RL, O'Brien RM, Cherrington AD | title = Insulin's direct hepatic effect explains the inhibition of glucose production caused by insulin secretion | journal = JCI Insight | volume = 2 | issue = 6 | pages = e91863 | date = March 2017 | pmid = 28352665 | pmc = 5358484 | doi = 10.1172/jci.insight.91863 }}</ref><ref name=":1">{{cite journal | vauthors = Jansson L, Barbu A, Bodin B, Drott CJ, Espes D, Gao X, Grapensparr L, Källskog Ö, Lau J, Liljebäck H, Palm F, Quach M, Sandberg M, Strömberg V, Ullsten S, Carlsson PO | title = Pancreatic islet blood flow and its measurement | journal = Upsala Journal of Medical Sciences | volume = 121 | issue = 2 | pages = 81–95 | date = May 2016 | pmid = 27124642 | doi = 10.3109/03009734.2016.1164769 | pmc = 4900068 }}</ref> The venous blood then eventually empties into the hepatic portal vein.<ref name=":1" />

In addition to the triggering pathway, the amplifying pathway can cause increased insulin secretion without a further increase in intracellular calcium levels. The amplifying pathway is modulated by byproducts of glucose metabolism along with various intracellular signaling pathways; [[incretin]] hormone signaling being one important example.<ref name="Kalwat_2017" /><ref>{{cite journal | vauthors = Holst JJ, Gasbjerg LS, Rosenkilde MM | title = The Role of Incretins on Insulin Function and Glucose Homeostasis | journal = Endocrinology | volume = 162 | issue = 7 | pages = bqab065 | date = July 2021 | pmid = 33782700 | pmc = 8168943 | doi = 10.1210/endocr/bqab065 }}</ref>

== Other hormones secreted ==
* [[C-peptide]], which is secreted into the bloodstream in equimolar quantities to insulin. C-peptide helps to prevent neuropathy and other vascular deterioration related symptoms of [[diabetes mellitus]].<ref name="pmid9228006">{{cite journal | vauthors = Ido Y, Vindigni A, Chang K, Stramm L, Chance R, Heath WF, DiMarchi RD, Di Cera E, Williamson JR | title = Prevention of vascular and neural dysfunction in diabetic rats by C-peptide | journal = Science | volume = 277 | issue = 5325 | pages = 563–566 | date = July 1997 | pmid = 9228006 | doi = 10.1126/science.277.5325.563 }}</ref> A practitioner would measure the levels of C-peptide to obtain an estimate for the viable beta cell mass.<ref>{{cite journal | vauthors = Hoogwerf BJ, Goetz FC | title = Urinary C-peptide: a simple measure of integrated insulin production with emphasis on the effects of body size, diet, and corticosteroids | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 56 | issue = 1 | pages = 60–67 | date = January 1983 | pmid = 6336620 | doi = 10.1210/jcem-56-1-60 }}</ref>
* [[Amylin]], also known as islet amyloid polypeptide (IAPP).<ref>{{cite journal | vauthors = Moore CX, Cooper GJ | title = Co-secretion of amylin and insulin from cultured islet beta-cells: modulation by nutrient secretagogues, islet hormones and hypoglycemic agents | journal = Biochemical and Biophysical Research Communications | volume = 179 | issue = 1 | pages = 1–9 | date = August 1991 | pmid = 1679326 | doi = 10.1016/0006-291X(91)91325-7 }}</ref> 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.<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" />

== 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.

== See also ==
{{Div col}}
* [[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]]
{{colend}}

== References ==
{{Reflist}}

{{Endocrine system anatomy}}
{{Authority control}}

{{DEFAULTSORT:Beta Cell}}
[[Category:Endocrine system anatomy]]
[[Category:Peptide hormone secreting cells]]