341:, 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.
462:
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.
212:
123:
454:
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.
176:, 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.
365:
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.
352:, 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
196:(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
242:
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
396:
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
364:
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
453:
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
219:
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).
465:
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
449:
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
281:
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
461:
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
474:
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
297:
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.
320:, 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.
329:
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:
420:
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
2398:
Lam, Carol & Jacobson, Daniel & Rankin, Matthew & Cox, Aaron & Kushner, Jake. (2017). β Cells
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441:, 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.
450:
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.
184:
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.
475:
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.
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400:
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.
1875:
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192:
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
1583:
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".
466:
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.
417:
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.
1548:
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".
1805:
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".
515:
126:
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).
2617:
310:, which is secreted into the bloodstream in equimolar quantities to insulin. C-peptide helps to prevent neuropathy and other vascular deterioration related symptoms of
2352:"Differentiation and transplantation of functional pancreatic beta cells generated from induced pluripotent stem cells derived from a type 1 diabetes mouse model"
2095:
Wang Z, Gleichmann H (January 1998). "GLUT2 in pancreatic islets: crucial target molecule in diabetes induced with multiple low doses of streptozotocin in mice".
1513:
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".
98:
1910:
Yu R, Nissen NN, Hendifar A, Tang L, Song YL, Chen YJ, Fan X (January 2017). "A Clinicopathological Study of
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1761:"Modestly increased beta cell apoptosis but no increased beta cell replication in recent-onset type 1 diabetic patients who died of diabetic ketoacidosis"
3014:
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3035:
286:, which allows calcium ions from outside the cell to diffuse in down their concentration gradient. When the calcium ions enter the cell, they cause
485:
2610:
490:
2466:
Bertram R, Sherman A, Satin LS (October 2007). "Metabolic and electrical oscillations: partners in controlling pulsatile insulin secretion".
200:. After maturation, these secretory vesicles hold insulin, C-peptide, and amylin until calcium triggers exocytosis of the granule contents.
403:
DPP-4 inhibitors block DPP-4 activity which increases postprandial incretin hormone concentration, therefore increasing insulin secretion.
910:
Andrali SS, Sampley ML, Vanderford NL, Ozcan S (October 2008). "Glucose regulation of insulin gene expression in pancreatic beta-cells".
3009:
239:
2603:
235:
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105:
225:
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Through translational processing, insulin is encoded as a 110 amino acid precursor but is secreted as a 51 amino acid protein.
1415:"The molecular mechanisms and pharmacotherapy of ATP-sensitive potassium channel gene mutations underlying neonatal diabetes"
1169:
Ashcroft FM, Rorsman P (February 1990). "ATP-sensitive K+ channels: a link between B-cell metabolism and insulin secretion".
283:
1119:"The central role of calcium in the effects of cytokines on beta-cell function: implications for type 1 and type 2 diabetes"
520:
93:
826:
Westermark P, Andersson A, Westermark GT (July 2011). "Islet amyloid polypeptide, islet amyloid, and diabetes mellitus".
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425:
imaging of calcium activity which correlates directly with insulin release. A final tool used in beta-cell research are
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338:
81:
2771:
2682:
1466:"Insulin's direct hepatic effect explains the inhibition of glucose production caused by insulin secretion"
314:. A practitioner would measure the levels of C-peptide to obtain an estimate for the viable beta cell mass.
2794:
2247:
Afelik S, Rovira M (April 2017). "Pancreatic β-cell regeneration: Facultative or dedicated progenitors?".
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505:
271:
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closure, and the opening of voltage gated calcium channels causing insulin granule fusion and exocytosis.
2550:
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275:
251:
193:
380:, but may be medically significant and even life-threatening due to recurrent and prolonged attacks of
2130:
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86:
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2422:
1369:
510:
244:
2132:"Morphological restructuring of myocardium during the early phase of experimental diabetes mellitus"
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156:. Constituting ~50–70% of cells in human islets, beta cells play a vital role in maintaining blood
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1935:
582:
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When the glucose concentration outside the cell is high, glucose molecules move into the cell by
2003:
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2920:
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2552:"Single-Cell Transcriptome Profiling of Human Pancreatic Islets in Health and Type 2 Diabetes"
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containing insulin to move to, and fuse with, the cell surface membrane, releasing insulin by
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145:
2501:
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349:
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1620:"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
141:
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1307:
Santulli G, Pagano G, Sardu C, Xie W, Reiken S, D'Ascia SL, et al. (May 2015).
586:
392:
Many drugs to combat diabetes are aimed at modifying the function of the beta cell.
17:
2992:
2958:
2948:
2886:
1939:
1720:"A choice of death--the signal-transduction of immune-mediated beta-cell apoptosis"
495:
381:
361:
2595:
559:
543:"Structural similarities and differences between the human and the mouse pancreas"
376:
is a rare tumor derived from the neoplasia of beta cells. Insulinomas are usually
1923:
1526:
861:
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211:
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2518:
2479:
1636:
1134:
981:
863:"β-Cell Control of Insulin Production During Starvation-Refeeding in Male Rats"
839:
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2021:
2004:
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500:
373:
291:
263:
2108:
1759:
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outside (as potassium ions carry a positive charge). At rest, this creates a
2744:
307:
197:
2585:
2536:
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2452:
2385:
2336:
2317:
2301:"Stem Cells Applications in Regenerative Medicine and Disease Therapeutics"
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1067:"Mechanisms of the amplifying pathway of insulin secretion in the β cell"
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353:
255:
221:
69:
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Studies have shown that it is possible to regenerate beta cells
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215:
The triggering pathway of glucose-stimulated insulin secretion
429:
experiments. Diabetes mellitus can be experimentally induced
220:
There are four key pieces to the triggering pathway of GSIS:
2468:
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148:
of
Langerhans responsible for the production and release of
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738:"The dynamic plasticity of insulin production in β-cells"
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1550:
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516:
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63:
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37:
32:
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1200:
1998:
1996:
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254:, down its concentration gradient through the
224:dependent glucose uptake, glucose metabolism,
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247:across the cell surface membrane of -70mV.
3015:List of human endocrine organs and actions
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1419:Pharmacogenomics and Personalized Medicine
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210:
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27:Type of cell found in pancreatic islets
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7:
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240:ATP-sensitive potassium ion channels
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397:less likely to cause hypoglycemia.
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25:
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3036:Peptide hormone secreting cells
2195:British Journal of Pharmacology
1071:Pharmacology & Therapeutics
75:endocrinocytus B; insulinocytus
294:into the hepatic portal vein.
284:voltage-gated calcium channels
262:to catalyze the first step of
236:Voltage-gated calcium channels
1:
1819:10.1016/s0163-8343(03)00055-0
1382:10.1016/S0006-3495(89)82669-4
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127:
2399:10.1210/jc.2016-3806.
2368:10.1089/scd.2011.0665
2189:King AJ (June 2012).
1737:10.1007/s001250100021
879:10.1210/en.2017-03120
828:Physiological Reviews
785:Wilcox G (May 2005).
325:Clinical significance
282:difference opens the
252:facilitated diffusion
214:
125:
2998:Organ of Zuckerkandl
2988:Enteroendocrine cell
2318:10.1155/2016/6940283
1562:10.1210/jcem-56-1-60
742:Molecular Metabolism
619:Molecular Metabolism
511:Islets of Langerhans
245:potential difference
18:Pancreatic beta cell
2777:Parafollicular cell
2427:2006BpJ....91.2082N
2415:Biophysical Journal
1374:1989BpJ....56..229K
1362:Biophysical Journal
1221:(1464): 2211–2225.
144:located within the
2921:Islets of pancreas
2695:Corticotropic cell
1432:10.2147/PGPM.S6969
1183:10.1042/bst0180109
924:10.1042/BJ20081029
217:
137:) are specialized
128:
87:H3.04.02.0.00026
3023:
3022:
2863:
2862:
2787:Parathyroid gland
2758:
2757:
2700:Gonadotropic cell
2673:Somatotropic cell
2513:(4): 385–394.e3.
2362:(14): 2642–2655.
2299:Mahla RS (2016).
2136:Anatomical Record
1771:(11): 2323–2331.
1730:(12): 2115–2133.
1521:(5325): 563–566.
1276:10.1172/JCI118308
1031:10.1111/jdi.12094
312:diabetes mellitus
229:
207:Insulin secretion
180:Insulin synthesis
146:pancreatic islets
120:
119:
115:
16:(Redirected from
3043:
2972:Corpora arenacea
2837:Zona reticularis
2832:Zona fasciculata
2827:Zona glomerulosa
2815:
2712:Chromophobe cell
2705:Thyrotropic cell
2641:
2628:endocrine system
2620:
2613:
2606:
2597:
2590:
2589:
2579:
2547:
2541:
2540:
2530:
2498:
2492:
2491:
2474:(4): E890–E900.
2463:
2457:
2456:
2446:
2421:(6): 2082–2096.
2406:
2400:
2396:
2390:
2389:
2379:
2347:
2341:
2340:
2330:
2320:
2296:
2281:
2280:
2244:
2229:
2228:
2218:
2186:
2180:
2179:
2161:
2151:
2149:10.1002/ar.23052
2127:
2121:
2120:
2092:
2086:
2085:
2075:
2065:
2041:
2035:
2034:
2024:
2015:(6): 1577–1596.
2000:
1985:
1984:
1974:
1950:
1944:
1943:
1907:
1901:
1900:
1872:
1866:
1865:
1837:
1831:
1830:
1802:
1791:
1790:
1780:
1756:
1750:
1749:
1739:
1715:
1709:
1708:
1698:
1666:
1660:
1659:
1649:
1639:
1615:
1609:
1608:
1580:
1574:
1573:
1545:
1539:
1538:
1510:
1504:
1503:
1493:
1461:
1455:
1454:
1444:
1434:
1410:
1404:
1403:
1393:
1353:
1347:
1346:
1336:
1325:10.1172/JCI79273
1319:(5): 1968–1978.
1304:
1298:
1297:
1287:
1270:(5): 2489–2495.
1255:
1249:
1248:
1238:
1206:
1195:
1194:
1166:
1157:
1156:
1146:
1114:
1105:
1104:
1094:
1062:
1053:
1052:
1042:
1010:
1004:
1003:
993:
961:
936:
935:
907:
901:
900:
890:
858:
852:
851:
823:
817:
816:
806:
782:
776:
775:
765:
733:
702:
701:
691:
674:(6): 1160–1171.
659:
653:
652:
642:
610:
591:
590:
572:
562:
538:
227:
112:edit on Wikidata
47:Pancreatic islet
30:
21:
3051:
3050:
3046:
3045:
3044:
3042:
3041:
3040:
3026:
3025:
3024:
3019:
2976:
2953:
2915:
2859:
2855:Chromaffin cell
2841:
2804:
2781:
2772:Follicular cell
2754:
2735:Median eminence
2716:
2653:Pars intermedia
2636:Pituitary gland
2630:
2626:Anatomy of the
2624:
2594:
2593:
2556:Cell Metabolism
2549:
2548:
2544:
2500:
2499:
2495:
2465:
2464:
2460:
2408:
2407:
2403:
2397:
2393:
2349:
2348:
2344:
2298:
2297:
2284:
2246:
2245:
2232:
2188:
2187:
2183:
2129:
2128:
2124:
2094:
2093:
2089:
2043:
2042:
2038:
2002:
2001:
1988:
1952:
1951:
1947:
1909:
1908:
1904:
1874:
1873:
1869:
1839:
1838:
1834:
1804:
1803:
1794:
1758:
1757:
1753:
1717:
1716:
1712:
1668:
1667:
1663:
1617:
1616:
1612:
1582:
1581:
1577:
1547:
1546:
1542:
1512:
1511:
1507:
1463:
1462:
1458:
1412:
1411:
1407:
1355:
1354:
1350:
1306:
1305:
1301:
1257:
1256:
1252:
1208:
1207:
1198:
1168:
1167:
1160:
1116:
1115:
1108:
1064:
1063:
1056:
1012:
1011:
1007:
963:
962:
939:
909:
908:
904:
860:
859:
855:
825:
824:
820:
784:
783:
779:
735:
734:
705:
661:
660:
656:
612:
611:
594:
553:(1): e1024405.
540:
539:
535:
530:
525:
481:
472:
470:Type 2 diabetes
447:
445:Type 1 diabetes
415:
410:
390:
371:
350:Type 2 diabetes
347:
345:Type 2 diabetes
336:
334:Type 1 diabetes
327:
304:
209:
182:
170:
116:
28:
23:
22:
15:
12:
11:
5:
3049:
3047:
3039:
3038:
3028:
3027:
3021:
3020:
3018:
3017:
3012:
3007:
3002:
3001:
3000:
2990:
2984:
2982:
2978:
2977:
2975:
2974:
2969:
2963:
2961:
2955:
2954:
2952:
2951:
2946:
2941:
2936:
2931:
2925:
2923:
2917:
2916:
2914:
2913:
2912:
2911:
2906:
2904:Granulosa cell
2901:
2891:
2890:
2889:
2884:
2873:
2871:
2865:
2864:
2861:
2860:
2858:
2857:
2851:
2849:
2843:
2842:
2840:
2839:
2834:
2829:
2823:
2821:
2812:
2806:
2805:
2803:
2802:
2797:
2791:
2789:
2783:
2782:
2780:
2779:
2774:
2768:
2766:
2760:
2759:
2756:
2755:
2753:
2752:
2750:Herring bodies
2747:
2742:
2737:
2732:
2726:
2724:
2718:
2717:
2715:
2714:
2709:
2708:
2707:
2702:
2697:
2687:
2686:
2685:
2680:
2678:Prolactin cell
2675:
2668:Acidophil cell
2665:
2660:
2658:Pars tuberalis
2655:
2649:
2647:
2638:
2632:
2631:
2625:
2623:
2622:
2615:
2608:
2600:
2592:
2591:
2562:(4): 593–607.
2542:
2493:
2458:
2401:
2391:
2342:
2311:(7): 6940283.
2282:
2230:
2201:(3): 877–894.
2181:
2142:(2): 396–407.
2122:
2087:
2036:
1986:
1965:(6): 386–399.
1945:
1902:
1883:(9): 908–917.
1867:
1832:
1813:(4): 246–252.
1792:
1751:
1710:
1681:(3): 183–193.
1661:
1610:
1575:
1540:
1505:
1456:
1405:
1368:(2): 229–242.
1348:
1299:
1250:
1196:
1177:(1): 109–111.
1158:
1129:(6): 481–490.
1106:
1054:
1025:(6): 511–516.
1005:
937:
902:
873:(2): 895–906.
853:
834:(3): 795–826.
818:
777:
748:(9): 958–973.
703:
654:
625:(9): 943–957.
592:
532:
531:
529:
526:
524:
523:
518:
513:
508:
503:
498:
493:
488:
482:
480:
477:
471:
468:
446:
443:
435:streptozotocin
414:
411:
409:
406:
405:
404:
401:
398:
389:
386:
370:
367:
346:
343:
335:
332:
326:
323:
322:
321:
315:
303:
300:
208:
205:
181:
178:
169:
166:
118:
117:
108:
102:
101:
96:
90:
89:
84:
78:
77:
72:
66:
65:
61:
60:
54:
50:
49:
44:
40:
39:
35:
34:
26:
24:
14:
13:
10:
9:
6:
4:
3:
2:
3048:
3037:
3034:
3033:
3031:
3016:
3013:
3011:
3008:
3006:
3003:
2999:
2996:
2995:
2994:
2991:
2989:
2986:
2985:
2983:
2979:
2973:
2970:
2968:
2965:
2964:
2962:
2960:
2956:
2950:
2947:
2945:
2942:
2940:
2937:
2935:
2932:
2930:
2927:
2926:
2924:
2922:
2918:
2910:
2909:Corpus luteum
2907:
2905:
2902:
2900:
2899:Theca interna
2897:
2896:
2895:
2892:
2888:
2885:
2883:
2880:
2879:
2878:
2875:
2874:
2872:
2870:
2866:
2856:
2853:
2852:
2850:
2848:
2844:
2838:
2835:
2833:
2830:
2828:
2825:
2824:
2822:
2820:
2816:
2813:
2811:
2810:Adrenal gland
2807:
2801:
2798:
2796:
2793:
2792:
2790:
2788:
2784:
2778:
2775:
2773:
2770:
2769:
2767:
2765:
2761:
2751:
2748:
2746:
2743:
2741:
2738:
2736:
2733:
2731:
2728:
2727:
2725:
2723:
2719:
2713:
2710:
2706:
2703:
2701:
2698:
2696:
2693:
2692:
2691:
2690:Basophil cell
2688:
2684:
2681:
2679:
2676:
2674:
2671:
2670:
2669:
2666:
2664:
2663:Pars distalis
2661:
2659:
2656:
2654:
2651:
2650:
2648:
2646:
2642:
2639:
2637:
2633:
2629:
2621:
2616:
2614:
2609:
2607:
2602:
2601:
2598:
2587:
2583:
2578:
2573:
2569:
2565:
2561:
2557:
2553:
2546:
2543:
2538:
2534:
2529:
2524:
2520:
2516:
2512:
2508:
2504:
2497:
2494:
2489:
2485:
2481:
2477:
2473:
2469:
2462:
2459:
2454:
2450:
2445:
2440:
2436:
2432:
2428:
2424:
2420:
2416:
2412:
2405:
2402:
2395:
2392:
2387:
2383:
2378:
2373:
2369:
2365:
2361:
2357:
2353:
2346:
2343:
2338:
2334:
2329:
2324:
2319:
2314:
2310:
2306:
2302:
2295:
2293:
2291:
2289:
2287:
2283:
2278:
2274:
2270:
2266:
2262:
2258:
2254:
2250:
2243:
2241:
2239:
2237:
2235:
2231:
2226:
2222:
2217:
2212:
2208:
2204:
2200:
2196:
2192:
2185:
2182:
2177:
2173:
2169:
2165:
2160:
2155:
2150:
2145:
2141:
2137:
2133:
2126:
2123:
2118:
2114:
2110:
2106:
2102:
2098:
2091:
2088:
2083:
2079:
2074:
2069:
2064:
2059:
2055:
2051:
2047:
2040:
2037:
2032:
2028:
2023:
2018:
2014:
2010:
2006:
1999:
1997:
1995:
1993:
1991:
1987:
1982:
1978:
1973:
1968:
1964:
1960:
1956:
1949:
1946:
1941:
1937:
1933:
1929:
1925:
1921:
1917:
1913:
1906:
1903:
1898:
1894:
1890:
1886:
1882:
1878:
1871:
1868:
1863:
1859:
1855:
1851:
1847:
1843:
1836:
1833:
1828:
1824:
1820:
1816:
1812:
1808:
1801:
1799:
1797:
1793:
1788:
1784:
1779:
1774:
1770:
1766:
1762:
1755:
1752:
1747:
1743:
1738:
1733:
1729:
1725:
1721:
1714:
1711:
1706:
1702:
1697:
1692:
1688:
1684:
1680:
1676:
1672:
1665:
1662:
1657:
1653:
1648:
1643:
1638:
1633:
1629:
1625:
1621:
1614:
1611:
1606:
1602:
1598:
1594:
1590:
1586:
1579:
1576:
1571:
1567:
1563:
1559:
1555:
1551:
1544:
1541:
1536:
1532:
1528:
1524:
1520:
1516:
1509:
1506:
1501:
1497:
1492:
1487:
1483:
1479:
1476:(6): e91863.
1475:
1471:
1467:
1460:
1457:
1452:
1448:
1443:
1438:
1433:
1428:
1424:
1420:
1416:
1409:
1406:
1401:
1397:
1392:
1387:
1383:
1379:
1375:
1371:
1367:
1363:
1359:
1352:
1349:
1344:
1340:
1335:
1330:
1326:
1322:
1318:
1314:
1310:
1303:
1300:
1295:
1291:
1286:
1281:
1277:
1273:
1269:
1265:
1261:
1254:
1251:
1246:
1242:
1237:
1232:
1228:
1224:
1220:
1216:
1212:
1205:
1203:
1201:
1197:
1192:
1188:
1184:
1180:
1176:
1172:
1165:
1163:
1159:
1154:
1150:
1145:
1140:
1136:
1132:
1128:
1124:
1120:
1113:
1111:
1107:
1102:
1098:
1093:
1088:
1084:
1080:
1076:
1072:
1068:
1061:
1059:
1055:
1050:
1046:
1041:
1036:
1032:
1028:
1024:
1020:
1016:
1009:
1006:
1001:
997:
992:
987:
983:
979:
975:
971:
967:
960:
958:
956:
954:
952:
950:
948:
946:
944:
942:
938:
933:
929:
925:
921:
917:
913:
906:
903:
898:
894:
889:
884:
880:
876:
872:
868:
867:Endocrinology
864:
857:
854:
849:
845:
841:
837:
833:
829:
822:
819:
814:
810:
805:
800:
796:
792:
788:
781:
778:
773:
769:
764:
759:
755:
751:
747:
743:
739:
732:
730:
728:
726:
724:
722:
720:
718:
716:
714:
712:
710:
708:
704:
699:
695:
690:
685:
681:
677:
673:
669:
665:
658:
655:
650:
646:
641:
636:
632:
628:
624:
620:
616:
609:
607:
605:
603:
601:
599:
597:
593:
588:
584:
580:
576:
571:
566:
561:
556:
552:
548:
544:
537:
534:
527:
522:
519:
517:
514:
512:
509:
507:
504:
502:
499:
497:
494:
492:
489:
487:
484:
483:
478:
476:
469:
467:
463:
460:
455:
451:
444:
442:
440:
436:
432:
428:
424:
418:
412:
407:
402:
399:
395:
394:
393:
387:
385:
383:
379:
375:
368:
366:
363:
359:
355:
351:
344:
342:
340:
333:
331:
324:
319:
316:
313:
309:
306:
305:
301:
299:
295:
293:
289:
285:
279:
277:
273:
269:
268:blood glucose
265:
261:
257:
253:
248:
246:
241:
237:
233:
231:
223:
213:
206:
204:
201:
199:
195:
191:
186:
179:
177:
175:
167:
165:
163:
159:
155:
151:
147:
143:
140:
136:
132:
124:
113:
107:
103:
100:
97:
95:
91:
88:
85:
83:
79:
76:
73:
71:
67:
62:
58:
55:
51:
48:
45:
41:
36:
31:
19:
2959:Pineal gland
2949:Epsilon cell
2933:
2887:Sertoli cell
2800:Oxyphil cell
2730:Pars nervosa
2559:
2555:
2545:
2510:
2507:Cell Systems
2506:
2496:
2471:
2467:
2461:
2418:
2414:
2404:
2394:
2359:
2355:
2345:
2308:
2304:
2252:
2248:
2198:
2194:
2184:
2139:
2135:
2125:
2103:(1): 50–56.
2100:
2096:
2090:
2053:
2049:
2039:
2012:
2009:Diabetologia
2008:
1962:
1958:
1948:
1918:(1): 48–56.
1915:
1911:
1905:
1880:
1876:
1870:
1845:
1841:
1835:
1810:
1806:
1768:
1765:Diabetologia
1764:
1754:
1727:
1724:Diabetologia
1723:
1713:
1678:
1674:
1664:
1627:
1623:
1613:
1588:
1584:
1578:
1556:(1): 60–67.
1553:
1549:
1543:
1518:
1514:
1508:
1473:
1469:
1459:
1422:
1418:
1408:
1365:
1361:
1351:
1316:
1312:
1302:
1267:
1263:
1253:
1218:
1214:
1174:
1170:
1126:
1123:Cell Calcium
1122:
1074:
1070:
1022:
1018:
1008:
976:(1): 25–53.
973:
969:
915:
911:
905:
870:
866:
856:
831:
827:
821:
797:(2): 19–39.
794:
790:
780:
745:
741:
671:
667:
657:
622:
618:
550:
546:
536:
496:Guangxitoxin
473:
464:
458:
456:
452:
448:
430:
426:
422:
419:
416:
391:
382:hypoglycemia
372:
362:muscle cells
348:
337:
328:
296:
280:
249:
234:
218:
202:
190:insulin gene
187:
183:
171:
134:
130:
129:
74:
3010:Development
2993:Paraganglia
2967:Pinealocyte
2882:Leydig cell
2159:10995/73117
1470:JCI Insight
1425:: 145–161.
918:(1): 1–10.
388:Medications
260:glucokinase
64:Identifiers
2944:Delta cell
2929:Alpha cell
2795:Chief cell
1877:Metabolism
1591:(1): 1–9.
528:References
501:Alpha cell
374:Insulinoma
369:Insulinoma
292:exocytosis
264:glycolysis
131:Beta cells
2934:Beta cell
2745:Pituicyte
2722:Posterior
2255:: 85–94.
2176:205412167
2056:(1): 19.
1077:: 17–30.
308:C-peptide
198:C-peptide
139:endocrine
59:secretion
33:Beta cell
3030:Category
3005:Placenta
2877:Testicle
2645:Anterior
2586:27667667
2537:27693023
2488:17666486
2453:16815907
2386:22512788
2337:27516776
2277:21795162
2269:27838399
2225:22352879
2168:25251897
2097:Diabetes
2082:27895534
2031:22526604
1981:17638715
1932:27984486
1912:Pancreas
1842:Diabetes
1827:12850656
1787:17805509
1746:11793013
1705:28368239
1656:34991585
1630:(1): 9.
1500:28352665
1451:23226049
1343:25844899
1245:16321791
1153:21944825
1101:28527919
1049:24843702
1000:22974359
932:18778246
897:29244064
848:21742788
813:16278749
772:28951821
698:22424227
649:28951820
587:17908732
579:26030186
479:See also
423:in vitro
408:Research
288:vesicles
174:hormones
168:Function
162:diabetes
53:Function
43:Location
2939:PP cell
2847:Medulla
2764:Thyroid
2577:5069352
2528:5092539
2444:1557567
2423:Bibcode
2377:3438879
2328:4969512
2216:3417415
2117:9421374
2073:5117600
1940:3723691
1897:1895955
1862:7589820
1696:5581966
1647:8740476
1605:1679326
1570:6336620
1535:9228006
1515:Science
1491:5358484
1442:3513215
1400:2673420
1391:1280472
1370:Bibcode
1334:4463204
1294:7593639
1236:1569593
1191:2185070
1144:3223281
1092:7269041
1040:4020243
991:3934755
888:5776497
804:1204764
763:5605729
689:5890906
640:5605733
570:4589993
459:in vivo
439:alloxan
431:in vivo
427:in vivo
358:adipose
278:ratio.
230:channel
158:glucose
150:insulin
135:β-cells
57:Insulin
38:Details
2869:Gonads
2819:Cortex
2584:
2574:
2535:
2525:
2486:
2451:
2441:
2384:
2374:
2335:
2325:
2275:
2267:
2223:
2213:
2174:
2166:
2115:
2080:
2070:
2029:
1979:
1938:
1930:
1895:
1860:
1825:
1785:
1744:
1703:
1693:
1654:
1644:
1603:
1568:
1533:
1498:
1488:
1449:
1439:
1398:
1388:
1341:
1331:
1292:
1285:185903
1282:
1243:
1233:
1189:
1151:
1141:
1099:
1089:
1047:
1037:
998:
988:
930:
895:
885:
846:
811:
801:
770:
760:
696:
686:
647:
637:
585:
577:
567:
547:Islets
378:benign
360:, and
318:Amylin
154:amylin
2981:Other
2894:Ovary
2740:Stalk
2273:S2CID
2172:S2CID
1936:S2CID
583:S2CID
354:liver
256:GLUT2
222:GLUT2
142:cells
110:[
99:85704
70:Latin
2582:PMID
2533:PMID
2484:PMID
2449:PMID
2382:PMID
2333:PMID
2309:2016
2265:PMID
2221:PMID
2164:PMID
2113:PMID
2078:PMID
2027:PMID
1977:PMID
1928:PMID
1893:PMID
1858:PMID
1823:PMID
1783:PMID
1742:PMID
1701:PMID
1652:PMID
1601:PMID
1566:PMID
1531:PMID
1496:PMID
1447:PMID
1396:PMID
1339:PMID
1290:PMID
1241:PMID
1187:PMID
1149:PMID
1097:PMID
1045:PMID
996:PMID
928:PMID
893:PMID
844:PMID
809:PMID
768:PMID
694:PMID
668:Cell
645:PMID
575:PMID
238:and
188:The
152:and
2572:PMC
2564:doi
2523:PMC
2515:doi
2476:doi
2472:293
2439:PMC
2431:doi
2372:PMC
2364:doi
2323:PMC
2313:doi
2257:doi
2253:445
2211:PMC
2203:doi
2199:166
2154:hdl
2144:doi
2140:298
2105:doi
2068:PMC
2058:doi
2017:doi
1967:doi
1963:147
1920:doi
1885:doi
1850:doi
1815:doi
1773:doi
1732:doi
1691:PMC
1683:doi
1642:PMC
1632:doi
1593:doi
1589:179
1558:doi
1523:doi
1519:277
1486:PMC
1478:doi
1437:PMC
1427:doi
1386:PMC
1378:doi
1329:PMC
1321:doi
1317:125
1280:PMC
1272:doi
1231:PMC
1223:doi
1219:360
1179:doi
1139:PMC
1131:doi
1087:PMC
1079:doi
1075:179
1035:PMC
1027:doi
986:PMC
978:doi
920:doi
916:415
883:PMC
875:doi
871:159
836:doi
799:PMC
758:PMC
750:doi
684:PMC
676:doi
672:148
635:PMC
627:doi
565:PMC
555:doi
437:or
276:ADP
272:ATP
228:ATP
94:FMA
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