330:, 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 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. 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. However, these methods can be tedious and cumbersome to continuously perform on a daily basis.
451:
concluded. 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.
201:
112:
443:
the differentiation of stem cells into beta cells: the BMP4 pathway and the kinase C. Targeted manipulation of these two pathways has shown that it is possible to induce beta cell differentiation from stem cells. 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.
165:, 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 inhibit gastric emptying.
354:
remain within their normal range due to the decreased efficacy of insulin signaling. 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. 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.
341:, also known as non insulin dependent diabetes and as chronic hyperglycemia, is caused primarily by genetics and the development of metabolic syndrome. The beta cells can still secrete insulin but the body has developed a resistance and its response to insulin has declined. It is believed to be due to the decline of specific receptors on the surface of the
185:(RER). Inside the RER, the signal peptide is cleaved to form proinsulin. Then, folding of proinsulin occurs forming three disulfide bonds. Subsequent to protein folding, proinsulin is transported to the Golgi apparatus and enters immature insulin granules where proinsulin is cleaved to form insulin and
231:
are embedded in the plasma membrane of beta cells. These ATP-sensitive potassium ion channels are normally open and the calcium ion channels are normally closed. Potassium ions diffuse out of the cell, down their concentration gradient, making the inside of the cell more negative with respect to the
385:
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. Second-generation versions of sulfonylureas are shorter acting and
353:
which lose their ability to respond to insulin that circulates in the blood. In an effort to secrete enough insulin to overcome the increasing insulin resistance, the beta cells increase their function, size and number. Increased insulin secretion leads to hyperinsulinemia, but blood glucose levels
442:
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. Two key signal pathways have been shown to play a vital role in
208:
In beta cells, insulin release is stimulated primarily by glucose present in the blood. As circulating glucose levels rise such as after ingesting a meal, insulin is secreted in a dose-dependent fashion. This system of release is commonly referred to as glucose-stimulated insulin secretion (GSIS).
454:
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
438:
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. Examples of the anomalies that arise from beta cells
270:
The ATP-sensitive potassium ion channels close when this ratio rises. This means that potassium ions can no longer diffuse out of the cell. As a result, the potential difference across the membrane becomes more positive (as potassium ions accumulate inside the cell). This change in potential
450:
in some animal models. 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
463:
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. Another topic of interest for beta-cell physiologists is the mechanism of insulin pulsatility which has been well
286:
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.
309:, 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.
318:
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:
409:
For instance, transcriptomics have allowed researchers to comprehensively analyze gene transcription in beta-cells to look for genes linked to diabetes. A more common mechanism of analyzing cellular function is calcium imaging. Fluorescent dyes bind to calcium and allow
2387:
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.
430:, 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.
439:
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.
173:
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.
464:
investigated. 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.
1994:"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)"
389:
GLP-1 receptor agonists stimulate insulin secretion by simulating activation of the body's endogenous incretin system. The incretin system acts as an insulin secretion amplifying pathway.
1864:
Rudenski AS, Matthews DR, Levy JC, Turner RC (September 1991). "Understanding "insulin resistance": both glucose resistance and insulin resistance are required to model human diabetes".
181:
is first transcribed into mRNA and translated into preproinsulin. After translation, the preproinsulin precursor contains an N-terminal signal peptide that allows translocation into the
1572:
Moore CX, Cooper GJ (August 1991). "Co-secretion of amylin and insulin from cultured islet beta-cells: modulation by nutrient secretagogues, islet hormones and hypoglycemic agents".
455:
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.
406:
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.
1537:
Hoogwerf BJ, Goetz FC (January 1983). "Urinary C-peptide: a simple measure of integrated insulin production with emphasis on the effects of body size, diet, and corticosteroids".
1794:
Ciechanowski PS, Katon WJ, Russo JE, Hirsch IB (July–August 2003). "The relationship of depressive symptoms to symptom reporting, self-care and glucose control in diabetes".
115:
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).
299:, which is secreted into the bloodstream in equimolar quantities to insulin. C-peptide helps to prevent neuropathy and other vascular deterioration related symptoms of
2341:"Differentiation and transplantation of functional pancreatic beta cells generated from induced pluripotent stem cells derived from a type 1 diabetes mouse model"
2084:
Wang Z, Gleichmann H (January 1998). "GLUT2 in pancreatic islets: crucial target molecule in diabetes induced with multiple low doses of streptozotocin in mice".
1502:
Ido Y, Vindigni A, Chang K, Stramm L, Chance R, Heath WF, et al. (July 1997). "Prevention of vascular and neural dysfunction in diabetic rats by C-peptide".
87:
1899:
Yu R, Nissen NN, Hendifar A, Tang L, Song YL, Chen YJ, Fan X (January 2017). "A Clinicopathological Study of
Malignant Insulinoma in a Contemporary Series".
1750:"Modestly increased beta cell apoptosis but no increased beta cell replication in recent-onset type 1 diabetic patients who died of diabetic ketoacidosis"
504:
2606:
1829:"U.K. prospective diabetes study 16. Overview of 6 years' therapy of type II diabetes: a progressive disease. U.K. Prospective Diabetes Study Group".
275:, which allows calcium ions from outside the cell to diffuse in down their concentration gradient. When the calcium ions enter the cell, they cause
2455:
Bertram R, Sherman A, Satin LS (October 2007). "Metabolic and electrical oscillations: partners in controlling pulsatile insulin secretion".
189:. After maturation, these secretory vesicles hold insulin, C-peptide, and amylin until calcium triggers exocytosis of the granule contents.
392:
DPP-4 inhibitors block DPP-4 activity which increases postprandial incretin hormone concentration, therefore increasing insulin secretion.
899:
Andrali SS, Sampley ML, Vanderford NL, Ozcan S (October 2008). "Glucose regulation of insulin gene expression in pancreatic beta-cells".
3003:
3024:
604:"Human beta cell mass and function in diabetes: Recent advances in knowledge and technologies to understand disease pathogenesis"
474:
2599:
479:
192:
Through translational processing, insulin is encoded as a 110 amino acid precursor but is secreted as a 51 amino acid protein.
1404:"The molecular mechanisms and pharmacotherapy of ATP-sensitive potassium channel gene mutations underlying neonatal diabetes"
1158:
Ashcroft FM, Rorsman P (February 1990). "ATP-sensitive K+ channels: a link between B-cell metabolism and insulin secretion".
1108:"The central role of calcium in the effects of cytokines on beta-cell function: implications for type 1 and type 2 diabetes"
2998:
815:
Westermark P, Andersson A, Westermark GT (July 2011). "Islet amyloid polypeptide, islet amyloid, and diabetes mellitus".
228:
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imaging of calcium activity which correlates directly with insulin release. A final tool used in beta-cell research are
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224:
94:
214:
272:
509:
82:
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1455:"Insulin's direct hepatic effect explains the inhibition of glucose production caused by insulin secretion"
303:. A practitioner would measure the levels of C-peptide to obtain an estimate for the viable beta cell mass.
2236:
Afelik S, Rovira M (April 2017). "Pancreatic β-cell regeneration: Facultative or dedicated progenitors?".
1944:"Systematic review: comparative effectiveness and safety of oral medications for type 2 diabetes mellitus"
221:
closure, and the opening of voltage gated calcium channels causing insulin granule fusion and exocytosis.
2539:
Segerstolpe Å, Palasantza A, Eliasson P, Andersson EM, Andréasson AC, Sun X, et al. (October 2016).
2400:"Glucose modulates [Ca2+]i oscillations in pancreatic islets via ionic and glycolytic mechanisms"
2788:
369:, but may be medically significant and even life-threatening due to recurrent and prolonged attacks of
2119:
Danilova IG, Sarapultsev PA, Medvedeva SU, Gette IF, Bulavintceva TS, Sarapultsev AP (February 2015).
75:
2651:
2121:"Morphological restructuring of myocardium during the early phase of experimental diabetes mellitus"
327:
145:. Constituting ~50–70% of cells in human islets, beta cells play a vital role in maintaining blood
70:
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2671:
239:
When the glucose concentration outside the cell is high, glucose molecules move into the cell by
1992:
Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, et al. (June 2012).
955:"Regulation of insulin synthesis and secretion and pancreatic Beta-cell dysfunction in diabetes"
2783:
2398:
Nunemaker CS, Bertram R, Sherman A, Tsaneva-Atanasova K, Daniel CR, Satin LS (September 2006).
1347:"ATP-sensitive potassium channel and bursting in the pancreatic beta cell. A theoretical study"
1249:"Human and rat beta cells differ in glucose transporter but not in glucokinase gene expression"
1247:
De Vos A, Heimberg H, Quartier E, Huypens P, Bouwens L, Pipeleers D, Schuit F (November 1995).
494:
260:
2541:"Single-Cell Transcriptome Profiling of Human Pancreatic Islets in Health and Type 2 Diabetes"
279:
containing insulin to move to, and fuse with, the cell surface membrane, releasing insulin by
2490:
Muraro MJ, Dharmadhikari G, Grün D, Groen N, Dielen T, Jansen E, et al. (October 2016).
1942:
Bolen S, Feldman L, Vassy J, Wilson L, Yeh HC, Marinopoulos S, et al. (September 2007).
1607:
Sakran N, Graham Y, Pintar T, Yang W, Kassir R, Willigendael EM, et al. (January 2022).
264:
240:
182:
1960:
1943:
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2411:
1358:
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233:
1453:
Edgerton DS, Kraft G, Smith M, Farmer B, Williams PE, Coate KC, et al. (March 2017).
8:
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1204:
Philosophical
Transactions of the Royal Society of London. Series B, Biological Sciences
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1609:"The many faces of diabetes. Is there a need for re-classification? A narrative review"
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The function of beta cells is primarily centered around the synthesis and secretion of
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Santulli G, Pagano G, Sardu C, Xie W, Reiken S, D'Ascia SL, et al. (May 2015).
575:
381:
Many drugs to combat diabetes are aimed at modifying the function of the beta cell.
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2005:
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1709:"A choice of death--the signal-transduction of immune-mediated beta-cell apoptosis"
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127:
35:
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548:
532:"Structural similarities and differences between the human and the mouse pancreas"
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is a rare tumor derived from the neoplasia of beta cells. Insulinomas are usually
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2835:
2728:
2723:
2641:
2624:
1912:
1515:
850:
Boland BB, Brown C, Alarcon C, Demozay D, Grimsby JS, Rhodes CJ (February 2018).
742:
619:
338:
2423:
2339:
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2035:"An Automated Perifusion System for Modifying Cell Culture Conditions over Time"
1842:
1298:"Calcium release channel RyR2 regulates insulin release and glucose homeostasis"
2892:
2807:
2738:
2656:
2646:
2556:
2507:
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1123:
970:
852:"β-Cell Control of Insulin Production During Starvation-Refeeding in Male Rats"
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130:
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2010:
1993:
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2097:
1748:
Butler AE, Galasso R, Meier JJ, Basu R, Rizza RA, Butler PC (November 2007).
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outside (as potassium ions carry a positive charge). At rest, this creates a
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2947:
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2441:
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2290:"Stem Cells Applications in Regenerative Medicine and Disease Therapeutics"
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2019:
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1056:"Mechanisms of the amplifying pathway of insulin secretion in the β cell"
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100:
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Whitticar NB, Strahler EW, Rajan P, Kaya S, Nunemaker CS (2016-11-21).
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602:
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Ramadan JW, Steiner SR, O'Neill CM, Nunemaker CS (December 2011).
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45:
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Studies have shown that it is possible to regenerate beta cells
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306:
149:
levels. Problems with beta cells can lead to disorders such as
142:
204:
The triggering pathway of glucose-stimulated insulin secretion
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1991:
1246:
898:
814:
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experiments. Diabetes mellitus can be experimentally induced
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244:
210:
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There are four key pieces to the triggering pathway of GSIS:
58:
2489:
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American
Journal of Physiology. Endocrinology and Metabolism
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137:
of
Langerhans responsible for the production and release of
1004:"Glucose-stimulated insulin secretion: A newer perspective"
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1863:
2492:"A Single-Cell Transcriptome Atlas of the Human Pancreas"
849:
727:"The dynamic plasticity of insulin production in β-cells"
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601:
1941:
1747:
1706:
1606:
1501:
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1197:
653:"Diabetes mellitus and the β cell: the last ten years"
1200:"Glucose-sensing mechanisms in pancreatic beta-cells"
1002:
Komatsu M, Takei M, Ishii H, Sato Y (November 2013).
1001:
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levels and above. Metabolism of the glucose produces
1898:
1789:
1787:
1785:
1660:"Apoptosis of pancreatic β-cells in Type 1 diabetes"
1539:
The
Journal of Clinical Endocrinology and Metabolism
1198:
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529:
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2454:
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725:Boland BB, Rhodes CJ, Grimsby JS (September 2017).
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505:
List of distinct cell types in the adult human body
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1987:
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2180:"The use of animal models in diabetes research"
1707:Eizirik DL, Mandrup-Poulsen T (December 2001).
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530:Dolenšek J, Rupnik MS, Stožer A (2015-01-02).
255:, metabolism only occurs around physiological
243:, down its concentration gradient through the
213:dependent glucose uptake, glucose metabolism,
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236:across the cell surface membrane of -70mV.
3004:List of human endocrine organs and actions
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1408:Pharmacogenomics and Personalized Medicine
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1664:Bosnian Journal of Basic Medical Sciences
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953:Fu Z, Gilbert ER, Liu D (January 2013).
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1961:10.7326/0003-4819-147-6-200709180-00178
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475:Gastric inhibitory polypeptide receptor
16:Type of cell found in pancreatic islets
3017:
1657:
927:
773:
480:List of terms associated with diabetes
2588:
2294:International Journal of Cell Biology
2287:
1302:The Journal of Clinical Investigation
1253:The Journal of Clinical Investigation
651:Ashcroft FM, Rorsman P (March 2012).
2238:Molecular and Cellular Endocrinology
2177:
1054:Kalwat MA, Cobb MH (November 2017).
458:
433:
229:ATP-sensitive potassium ion channels
195:
168:
13:
1345:Keizer J, Magnus G (August 1989).
386:less likely to cause hypoglycemia.
333:
322:
247:transporter. Since beta cells use
14:
3036:
1008:Journal of Diabetes Investigation
2196:10.1111/j.1476-5381.2012.01911.x
1837:(11): 1249–1258. November 1995.
1160:Biochemical Society Transactions
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780:The Clinical Biochemist. Reviews
776:"Insulin and insulin resistance"
95:Anatomical terms of microanatomy
3025:Peptide hormone secreting cells
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2184:British Journal of Pharmacology
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1060:Pharmacology & Therapeutics
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64:endocrinocytus B; insulinocytus
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808:
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283:into the hepatic portal vein.
273:voltage-gated calcium channels
251:to catalyze the first step of
225:Voltage-gated calcium channels
1:
1808:10.1016/s0163-8343(03)00055-0
1371:10.1016/S0006-3495(89)82669-4
549:10.1080/19382014.2015.1024405
516:
510:Pancreatic beta cell function
357:
263:, which increases the ATP to
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620:10.1016/j.molmet.2017.06.019
7:
2424:10.1529/biophysj.106.087296
1948:Annals of Internal Medicine
1843:10.2337/diabetes.44.11.1249
1796:General Hospital Psychiatry
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396:
183:rough endoplasmic reticulum
156:
10:
3041:
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2508:10.1016/j.cels.2016.09.002
2469:10.1152/ajpendo.00359.2007
2345:Stem Cells and Development
1626:10.1186/s12902-021-00927-y
1124:10.1016/j.ceca.2011.08.005
971:10.2174/157339913804143225
829:10.1152/physrev.00042.2009
669:10.1016/j.cell.2012.02.010
2969:
2946:
2908:
2856:
2834:
2806:
2797:
2774:
2751:
2709:
2632:
2623:
2250:10.1016/j.mce.2016.11.008
2052:10.1186/s12575-016-0049-7
2011:10.1007/s00125-012-2534-0
1767:10.1007/s00125-007-0794-x
1471:10.1172/jci.insight.91863
1402:Lang V, Light PE (2010).
422:for research purposes by
93:
81:
69:
57:
52:
41:
31:
26:
21:
2098:10.2337/diabetes.47.1.50
1676:10.17305/bjbms.2017.1961
1658:Tomita T (August 2017).
959:Current Diabetes Reviews
328:Type 1 diabetes mellitus
2672:Somatomammotrophic cell
1613:BMC Endocrine Disorders
901:The Biochemical Journal
402:Experimental techniques
291:Other hormones secreted
1216:10.1098/rstb.2005.1762
495:Pancreatic development
205:
116:
2388:10.1210/jc.2016-3806.
2357:10.1089/scd.2011.0665
2178:King AJ (June 2012).
1726:10.1007/s001250100021
868:10.1210/en.2017-03120
817:Physiological Reviews
774:Wilcox G (May 2005).
314:Clinical significance
271:difference opens the
241:facilitated diffusion
203:
114:
2987:Organ of Zuckerkandl
2977:Enteroendocrine cell
2307:10.1155/2016/6940283
1551:10.1210/jcem-56-1-60
731:Molecular Metabolism
608:Molecular Metabolism
500:Islets of Langerhans
234:potential difference
2766:Parafollicular cell
2416:2006BpJ....91.2082N
2404:Biophysical Journal
1363:1989BpJ....56..229K
1351:Biophysical Journal
1210:(1464): 2211–2225.
133:located within the
2910:Islets of pancreas
2684:Corticotropic cell
1421:10.2147/PGPM.S6969
1172:10.1042/bst0180109
913:10.1042/BJ20081029
206:
126:) are specialized
117:
76:H3.04.02.0.00026
3012:
3011:
2852:
2851:
2776:Parathyroid gland
2747:
2746:
2689:Gonadotropic cell
2662:Somatotropic cell
2502:(4): 385–394.e3.
2351:(14): 2642–2655.
2288:Mahla RS (2016).
2125:Anatomical Record
1760:(11): 2323–2331.
1719:(12): 2115–2133.
1510:(5325): 563–566.
1265:10.1172/JCI118308
1020:10.1111/jdi.12094
301:diabetes mellitus
218:
196:Insulin secretion
169:Insulin synthesis
135:pancreatic islets
109:
108:
104:
3032:
2961:Corpora arenacea
2826:Zona reticularis
2821:Zona fasciculata
2816:Zona glomerulosa
2804:
2803:
2701:Chromophobe cell
2694:Thyrotropic cell
2630:
2629:
2617:endocrine system
2609:
2602:
2595:
2586:
2585:
2579:
2578:
2568:
2536:
2530:
2529:
2519:
2487:
2481:
2480:
2463:(4): E890–E900.
2452:
2446:
2445:
2435:
2410:(6): 2082–2096.
2395:
2389:
2385:
2379:
2378:
2368:
2336:
2330:
2329:
2319:
2309:
2285:
2270:
2269:
2233:
2218:
2217:
2207:
2175:
2169:
2168:
2150:
2140:
2138:10.1002/ar.23052
2116:
2110:
2109:
2081:
2075:
2074:
2064:
2054:
2030:
2024:
2023:
2013:
2004:(6): 1577–1596.
1989:
1974:
1973:
1963:
1939:
1933:
1932:
1896:
1890:
1889:
1861:
1855:
1854:
1826:
1820:
1819:
1791:
1780:
1779:
1769:
1745:
1739:
1738:
1728:
1704:
1698:
1697:
1687:
1655:
1649:
1648:
1638:
1628:
1604:
1598:
1597:
1569:
1563:
1562:
1534:
1528:
1527:
1499:
1493:
1492:
1482:
1450:
1444:
1443:
1433:
1423:
1399:
1393:
1392:
1382:
1342:
1336:
1335:
1325:
1314:10.1172/JCI79273
1308:(5): 1968–1978.
1293:
1287:
1286:
1276:
1259:(5): 2489–2495.
1244:
1238:
1237:
1227:
1195:
1184:
1183:
1155:
1146:
1145:
1135:
1103:
1094:
1093:
1083:
1051:
1042:
1041:
1031:
999:
993:
992:
982:
950:
925:
924:
896:
890:
889:
879:
847:
841:
840:
812:
806:
805:
795:
771:
765:
764:
754:
722:
691:
690:
680:
663:(6): 1160–1171.
648:
642:
641:
631:
599:
580:
579:
561:
551:
527:
216:
101:edit on Wikidata
98:
36:Pancreatic islet
19:
18:
3040:
3039:
3035:
3034:
3033:
3031:
3030:
3029:
3015:
3014:
3013:
3008:
2965:
2942:
2904:
2848:
2844:Chromaffin cell
2830:
2793:
2770:
2761:Follicular cell
2743:
2724:Median eminence
2705:
2642:Pars intermedia
2625:Pituitary gland
2619:
2615:Anatomy of the
2613:
2583:
2582:
2545:Cell Metabolism
2537:
2533:
2488:
2484:
2453:
2449:
2396:
2392:
2386:
2382:
2337:
2333:
2286:
2273:
2234:
2221:
2176:
2172:
2117:
2113:
2082:
2078:
2031:
2027:
1990:
1977:
1940:
1936:
1897:
1893:
1862:
1858:
1828:
1827:
1823:
1792:
1783:
1746:
1742:
1705:
1701:
1656:
1652:
1605:
1601:
1570:
1566:
1535:
1531:
1500:
1496:
1451:
1447:
1400:
1396:
1343:
1339:
1294:
1290:
1245:
1241:
1196:
1187:
1156:
1149:
1104:
1097:
1052:
1045:
1000:
996:
951:
928:
897:
893:
848:
844:
813:
809:
772:
768:
723:
694:
649:
645:
600:
583:
542:(1): e1024405.
528:
524:
519:
514:
470:
461:
459:Type 2 diabetes
436:
434:Type 1 diabetes
404:
399:
379:
360:
339:Type 2 diabetes
336:
334:Type 2 diabetes
325:
323:Type 1 diabetes
316:
293:
198:
171:
159:
105:
17:
12:
11:
5:
3038:
3028:
3027:
3010:
3009:
3007:
3006:
3001:
2996:
2991:
2990:
2989:
2979:
2973:
2971:
2967:
2966:
2964:
2963:
2958:
2952:
2950:
2944:
2943:
2941:
2940:
2935:
2930:
2925:
2920:
2914:
2912:
2906:
2905:
2903:
2902:
2901:
2900:
2895:
2893:Granulosa cell
2890:
2880:
2879:
2878:
2873:
2862:
2860:
2854:
2853:
2850:
2849:
2847:
2846:
2840:
2838:
2832:
2831:
2829:
2828:
2823:
2818:
2812:
2810:
2801:
2795:
2794:
2792:
2791:
2786:
2780:
2778:
2772:
2771:
2769:
2768:
2763:
2757:
2755:
2749:
2748:
2745:
2744:
2742:
2741:
2739:Herring bodies
2736:
2731:
2726:
2721:
2715:
2713:
2707:
2706:
2704:
2703:
2698:
2697:
2696:
2691:
2686:
2676:
2675:
2674:
2669:
2667:Prolactin cell
2664:
2657:Acidophil cell
2654:
2649:
2647:Pars tuberalis
2644:
2638:
2636:
2627:
2621:
2620:
2612:
2611:
2604:
2597:
2589:
2581:
2580:
2551:(4): 593–607.
2531:
2482:
2447:
2390:
2380:
2331:
2300:(7): 6940283.
2271:
2219:
2190:(3): 877–894.
2170:
2131:(2): 396–407.
2111:
2076:
2025:
1975:
1954:(6): 386–399.
1934:
1891:
1872:(9): 908–917.
1856:
1821:
1802:(4): 246–252.
1781:
1740:
1699:
1670:(3): 183–193.
1650:
1599:
1564:
1529:
1494:
1445:
1394:
1357:(2): 229–242.
1337:
1288:
1239:
1185:
1166:(1): 109–111.
1147:
1118:(6): 481–490.
1095:
1043:
1014:(6): 511–516.
994:
926:
891:
862:(2): 895–906.
842:
823:(3): 795–826.
807:
766:
737:(9): 958–973.
692:
643:
614:(9): 943–957.
581:
521:
520:
518:
515:
513:
512:
507:
502:
497:
492:
487:
482:
477:
471:
469:
466:
460:
457:
435:
432:
424:streptozotocin
403:
400:
398:
395:
394:
393:
390:
387:
378:
375:
359:
356:
335:
332:
324:
321:
315:
312:
311:
310:
304:
292:
289:
197:
194:
170:
167:
158:
155:
107:
106:
97:
91:
90:
85:
79:
78:
73:
67:
66:
61:
55:
54:
50:
49:
43:
39:
38:
33:
29:
28:
24:
23:
15:
9:
6:
4:
3:
2:
3037:
3026:
3023:
3022:
3020:
3005:
3002:
3000:
2997:
2995:
2992:
2988:
2985:
2984:
2983:
2980:
2978:
2975:
2974:
2972:
2968:
2962:
2959:
2957:
2954:
2953:
2951:
2949:
2945:
2939:
2936:
2934:
2931:
2929:
2926:
2924:
2921:
2919:
2916:
2915:
2913:
2911:
2907:
2899:
2898:Corpus luteum
2896:
2894:
2891:
2889:
2888:Theca interna
2886:
2885:
2884:
2881:
2877:
2874:
2872:
2869:
2868:
2867:
2864:
2863:
2861:
2859:
2855:
2845:
2842:
2841:
2839:
2837:
2833:
2827:
2824:
2822:
2819:
2817:
2814:
2813:
2811:
2809:
2805:
2802:
2800:
2799:Adrenal gland
2796:
2790:
2787:
2785:
2782:
2781:
2779:
2777:
2773:
2767:
2764:
2762:
2759:
2758:
2756:
2754:
2750:
2740:
2737:
2735:
2732:
2730:
2727:
2725:
2722:
2720:
2717:
2716:
2714:
2712:
2708:
2702:
2699:
2695:
2692:
2690:
2687:
2685:
2682:
2681:
2680:
2679:Basophil cell
2677:
2673:
2670:
2668:
2665:
2663:
2660:
2659:
2658:
2655:
2653:
2652:Pars distalis
2650:
2648:
2645:
2643:
2640:
2639:
2637:
2635:
2631:
2628:
2626:
2622:
2618:
2610:
2605:
2603:
2598:
2596:
2591:
2590:
2587:
2576:
2572:
2567:
2562:
2558:
2554:
2550:
2546:
2542:
2535:
2527:
2523:
2518:
2513:
2509:
2505:
2501:
2497:
2493:
2486:
2478:
2474:
2470:
2466:
2462:
2458:
2451:
2443:
2439:
2434:
2429:
2425:
2421:
2417:
2413:
2409:
2405:
2401:
2394:
2384:
2376:
2372:
2367:
2362:
2358:
2354:
2350:
2346:
2342:
2335:
2327:
2323:
2318:
2313:
2308:
2303:
2299:
2295:
2291:
2284:
2282:
2280:
2278:
2276:
2267:
2263:
2259:
2255:
2251:
2247:
2243:
2239:
2232:
2230:
2228:
2226:
2224:
2215:
2211:
2206:
2201:
2197:
2193:
2189:
2185:
2181:
2174:
2166:
2162:
2158:
2154:
2149:
2144:
2139:
2134:
2130:
2126:
2122:
2115:
2107:
2103:
2099:
2095:
2091:
2087:
2080:
2072:
2068:
2063:
2058:
2053:
2048:
2044:
2040:
2036:
2029:
2021:
2017:
2012:
2007:
2003:
1999:
1995:
1988:
1986:
1984:
1982:
1980:
1971:
1967:
1962:
1957:
1953:
1949:
1945:
1938:
1930:
1926:
1922:
1918:
1914:
1910:
1906:
1902:
1895:
1887:
1883:
1879:
1875:
1871:
1867:
1860:
1852:
1848:
1844:
1840:
1836:
1832:
1825:
1817:
1813:
1809:
1805:
1801:
1797:
1790:
1788:
1786:
1777:
1773:
1768:
1763:
1759:
1755:
1751:
1744:
1736:
1732:
1727:
1722:
1718:
1714:
1710:
1703:
1695:
1691:
1686:
1681:
1677:
1673:
1669:
1665:
1661:
1654:
1646:
1642:
1637:
1632:
1627:
1622:
1618:
1614:
1610:
1603:
1595:
1591:
1587:
1583:
1579:
1575:
1568:
1560:
1556:
1552:
1548:
1544:
1540:
1533:
1525:
1521:
1517:
1513:
1509:
1505:
1498:
1490:
1486:
1481:
1476:
1472:
1468:
1465:(6): e91863.
1464:
1460:
1456:
1449:
1441:
1437:
1432:
1427:
1422:
1417:
1413:
1409:
1405:
1398:
1390:
1386:
1381:
1376:
1372:
1368:
1364:
1360:
1356:
1352:
1348:
1341:
1333:
1329:
1324:
1319:
1315:
1311:
1307:
1303:
1299:
1292:
1284:
1280:
1275:
1270:
1266:
1262:
1258:
1254:
1250:
1243:
1235:
1231:
1226:
1221:
1217:
1213:
1209:
1205:
1201:
1194:
1192:
1190:
1181:
1177:
1173:
1169:
1165:
1161:
1154:
1152:
1143:
1139:
1134:
1129:
1125:
1121:
1117:
1113:
1109:
1102:
1100:
1091:
1087:
1082:
1077:
1073:
1069:
1065:
1061:
1057:
1050:
1048:
1039:
1035:
1030:
1025:
1021:
1017:
1013:
1009:
1005:
998:
990:
986:
981:
976:
972:
968:
964:
960:
956:
949:
947:
945:
943:
941:
939:
937:
935:
933:
931:
922:
918:
914:
910:
906:
902:
895:
887:
883:
878:
873:
869:
865:
861:
857:
856:Endocrinology
853:
846:
838:
834:
830:
826:
822:
818:
811:
803:
799:
794:
789:
785:
781:
777:
770:
762:
758:
753:
748:
744:
740:
736:
732:
728:
721:
719:
717:
715:
713:
711:
709:
707:
705:
703:
701:
699:
697:
688:
684:
679:
674:
670:
666:
662:
658:
654:
647:
639:
635:
630:
625:
621:
617:
613:
609:
605:
598:
596:
594:
592:
590:
588:
586:
577:
573:
569:
565:
560:
555:
550:
545:
541:
537:
533:
526:
522:
511:
508:
506:
503:
501:
498:
496:
493:
491:
488:
486:
483:
481:
478:
476:
473:
472:
465:
456:
452:
449:
444:
440:
431:
429:
425:
421:
417:
413:
407:
391:
388:
384:
383:
382:
374:
372:
368:
364:
355:
352:
348:
344:
340:
331:
329:
320:
308:
305:
302:
298:
295:
294:
288:
284:
282:
278:
274:
268:
266:
262:
258:
257:blood glucose
254:
250:
246:
242:
237:
235:
230:
226:
222:
220:
212:
202:
193:
190:
188:
184:
180:
175:
166:
164:
154:
152:
148:
144:
140:
136:
132:
129:
125:
121:
113:
102:
96:
92:
89:
86:
84:
80:
77:
74:
72:
68:
65:
62:
60:
56:
51:
47:
44:
40:
37:
34:
30:
25:
20:
2948:Pineal gland
2938:Epsilon cell
2922:
2876:Sertoli cell
2789:Oxyphil cell
2719:Pars nervosa
2548:
2544:
2534:
2499:
2496:Cell Systems
2495:
2485:
2460:
2456:
2450:
2407:
2403:
2393:
2383:
2348:
2344:
2334:
2297:
2293:
2241:
2237:
2187:
2183:
2173:
2128:
2124:
2114:
2092:(1): 50–56.
2089:
2085:
2079:
2042:
2038:
2028:
2001:
1998:Diabetologia
1997:
1951:
1947:
1937:
1907:(1): 48–56.
1904:
1900:
1894:
1869:
1865:
1859:
1834:
1830:
1824:
1799:
1795:
1757:
1754:Diabetologia
1753:
1743:
1716:
1713:Diabetologia
1712:
1702:
1667:
1663:
1653:
1616:
1612:
1602:
1577:
1573:
1567:
1545:(1): 60–67.
1542:
1538:
1532:
1507:
1503:
1497:
1462:
1458:
1448:
1411:
1407:
1397:
1354:
1350:
1340:
1305:
1301:
1291:
1256:
1252:
1242:
1207:
1203:
1163:
1159:
1115:
1112:Cell Calcium
1111:
1063:
1059:
1011:
1007:
997:
965:(1): 25–53.
962:
958:
904:
900:
894:
859:
855:
845:
820:
816:
810:
786:(2): 19–39.
783:
779:
769:
734:
730:
660:
656:
646:
611:
607:
539:
535:
525:
485:Guangxitoxin
462:
453:
447:
445:
441:
437:
419:
415:
411:
408:
405:
380:
371:hypoglycemia
361:
351:muscle cells
337:
326:
317:
285:
269:
238:
223:
207:
191:
179:insulin gene
176:
172:
160:
123:
119:
118:
63:
2999:Development
2982:Paraganglia
2956:Pinealocyte
2871:Leydig cell
2148:10995/73117
1459:JCI Insight
1414:: 145–161.
907:(1): 1–10.
377:Medications
249:glucokinase
53:Identifiers
2933:Delta cell
2918:Alpha cell
2784:Chief cell
1866:Metabolism
1580:(1): 1–9.
517:References
490:Alpha cell
363:Insulinoma
358:Insulinoma
281:exocytosis
253:glycolysis
120:Beta cells
2923:Beta cell
2734:Pituicyte
2711:Posterior
2244:: 85–94.
2165:205412167
2045:(1): 19.
1066:: 17–30.
297:C-peptide
187:C-peptide
128:endocrine
48:secretion
22:Beta cell
3019:Category
2994:Placenta
2866:Testicle
2634:Anterior
2575:27667667
2526:27693023
2477:17666486
2442:16815907
2375:22512788
2326:27516776
2266:21795162
2258:27838399
2214:22352879
2157:25251897
2086:Diabetes
2071:27895534
2020:22526604
1970:17638715
1921:27984486
1901:Pancreas
1831:Diabetes
1816:12850656
1776:17805509
1735:11793013
1694:28368239
1645:34991585
1619:(1): 9.
1489:28352665
1440:23226049
1332:25844899
1234:16321791
1142:21944825
1090:28527919
1038:24843702
989:22974359
921:18778246
886:29244064
837:21742788
802:16278749
761:28951821
687:22424227
638:28951820
576:17908732
568:26030186
468:See also
412:in vitro
397:Research
277:vesicles
163:hormones
157:Function
151:diabetes
42:Function
32:Location
2928:PP cell
2836:Medulla
2753:Thyroid
2566:5069352
2517:5092539
2433:1557567
2412:Bibcode
2366:3438879
2317:4969512
2205:3417415
2106:9421374
2062:5117600
1929:3723691
1886:1895955
1851:7589820
1685:5581966
1636:8740476
1594:1679326
1559:6336620
1524:9228006
1504:Science
1480:5358484
1431:3513215
1389:2673420
1380:1280472
1359:Bibcode
1323:4463204
1283:7593639
1225:1569593
1180:2185070
1133:3223281
1081:7269041
1029:4020243
980:3934755
877:5776497
793:1204764
752:5605729
678:5890906
629:5605733
559:4589993
448:in vivo
428:alloxan
420:in vivo
416:in vivo
347:adipose
267:ratio.
219:channel
147:glucose
139:insulin
124:β-cells
46:Insulin
27:Details
2858:Gonads
2808:Cortex
2573:
2563:
2524:
2514:
2475:
2440:
2430:
2373:
2363:
2324:
2314:
2264:
2256:
2212:
2202:
2163:
2155:
2104:
2069:
2059:
2018:
1968:
1927:
1919:
1884:
1849:
1814:
1774:
1733:
1692:
1682:
1643:
1633:
1592:
1557:
1522:
1487:
1477:
1438:
1428:
1387:
1377:
1330:
1320:
1281:
1274:185903
1271:
1232:
1222:
1178:
1140:
1130:
1088:
1078:
1036:
1026:
987:
977:
919:
884:
874:
835:
800:
790:
759:
749:
685:
675:
636:
626:
574:
566:
556:
536:Islets
367:benign
349:, and
307:Amylin
143:amylin
2970:Other
2883:Ovary
2729:Stalk
2262:S2CID
2161:S2CID
1925:S2CID
572:S2CID
343:liver
245:GLUT2
211:GLUT2
131:cells
99:[
88:85704
59:Latin
2571:PMID
2522:PMID
2473:PMID
2438:PMID
2371:PMID
2322:PMID
2298:2016
2254:PMID
2210:PMID
2153:PMID
2102:PMID
2067:PMID
2016:PMID
1966:PMID
1917:PMID
1882:PMID
1847:PMID
1812:PMID
1772:PMID
1731:PMID
1690:PMID
1641:PMID
1590:PMID
1555:PMID
1520:PMID
1485:PMID
1436:PMID
1385:PMID
1328:PMID
1279:PMID
1230:PMID
1176:PMID
1138:PMID
1086:PMID
1034:PMID
985:PMID
917:PMID
882:PMID
833:PMID
798:PMID
757:PMID
683:PMID
657:Cell
634:PMID
564:PMID
227:and
177:The
141:and
2561:PMC
2553:doi
2512:PMC
2504:doi
2465:doi
2461:293
2428:PMC
2420:doi
2361:PMC
2353:doi
2312:PMC
2302:doi
2246:doi
2242:445
2200:PMC
2192:doi
2188:166
2143:hdl
2133:doi
2129:298
2094:doi
2057:PMC
2047:doi
2006:doi
1956:doi
1952:147
1909:doi
1874:doi
1839:doi
1804:doi
1762:doi
1721:doi
1680:PMC
1672:doi
1631:PMC
1621:doi
1582:doi
1578:179
1547:doi
1512:doi
1508:277
1475:PMC
1467:doi
1426:PMC
1416:doi
1375:PMC
1367:doi
1318:PMC
1310:doi
1306:125
1269:PMC
1261:doi
1220:PMC
1212:doi
1208:360
1168:doi
1128:PMC
1120:doi
1076:PMC
1068:doi
1064:179
1024:PMC
1016:doi
975:PMC
967:doi
909:doi
905:415
872:PMC
864:doi
860:159
825:doi
788:PMC
747:PMC
739:doi
673:PMC
665:doi
661:148
624:PMC
616:doi
554:PMC
544:doi
426:or
265:ADP
261:ATP
217:ATP
83:FMA
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