Alpha-, Delta- and PP-cells: Are They the Architectural Cornerstones of Islet Structure and Co-ordination?

Journal of Histochemistry and Cytochemistry

Volumn 63, Issue 8, 2015, Pages 575-591

  Brereton, Melissa F ^a   Vergari, Elisa ^b   Zhang, Quan ^b   Clark, Anne ^b  

^a UNIVERSITY OF OXFORD   (United Kingdom)

^b UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

communication; exocytosis; glucagon; granule; insulin; intra islet signaling; non cell; paracrine; PP; somatostatin

Indexed keywords

GLUCAGON; GLUCAGON RECEPTOR; INSULIN; PANCREAS POLYPEPTIDE; SOMATOSTATIN 14; SOMATOSTATIN 28;

ARTICLE; CELL COMMUNICATION; CELL DIFFERENTIATION; CELL FUNCTION; CELL STRUCTURE; CHEMICAL INDUSTRY; DIABETES MELLITUS; GLUCAGON RELEASE; HUMAN; NONHUMAN; PANCREAS ISLET ALPHA CELL; PANCREAS ISLET BETA CELL; PANCREATIC POLYPEPTIDE SECRETING CELL; PRIORITY JOURNAL; ANATOMY AND HISTOLOGY; ANIMAL; CYTOLOGY; ELECTRON MICROSCOPY; METABOLISM; PANCREAS ISLET; ULTRASTRUCTURE;

PRIMATES; RODENTIA;

ANIMALS; HUMANS; ISLETS OF LANGERHANS; MICROSCOPY, ELECTRON;

EID: 84938316421     PISSN: 00221554     EISSN: 15515044     Source Type: Journal    
DOI: 10.1369/0022155415583535     Document Type: Article

References (133)

1. F.AragonM.KaracaA.NovialsR.MaldonadoP.MaechlerB.Rubi (2015). Pancreatic polypeptide regulates glucagon release through PPYR1 receptors expressed in mouse and human alpha-cells. Biochim Biophys Acta1850:343-351.
2. A.ArimuraH.SatoA.DupontN.NishiA.V.Schally (1975). Somatostatin: abundance of immunoreactive hormone in rat stomach and pancreas. Science189:1007-1009.
3. S.BargJ.GalvanovskisS.O.GopelP.RorsmanL.Eliasson (2000). Tight coupling between electrical activity and exocytosis in mouse glucagon-secreting alpha-cells. Diabetes49:1500-1510.
4. A.D.BaronL.SchaefferP.ShraggO.G.Kolterman (1987). Role of hyperglucagonemia in maintenance of increased rates of hepatic glucose output in type II diabetics. Diabetes36:274-283.
5. D.G.BaskinK.C.GorrayW.Y.Fujimoto (1984). Immunocytochemical identification of cells containing insulin, glucagon, somatostatin, and pancreatic polypeptide in the islets of Langerhans of the guinea pig pancreas with light and electron microscopy. Anat Rec208:567-578.
6. J.A.BastidasN.F.CouseC.J.YeoR.E.SchmiegJr.D.K.AndersenR.L.GingerichM.J.Zinner (1990). The effect of pancreatic polypeptide infusion on glucose tolerance and insulin response in longitudinally studied pancreatitis-induced diabetes. Surgery107:661-668.
7. A.BertsA.BallG.DryseliusE.GylfeB.Hellman (1996). Glucose stimulation of somatostatin-producing islet cells involves oscillatory Ca2+ signaling. Endocrinology137:693-697.
8. S.Bonner-WeirL.Orci (1982). New perspectives on the microvasculature of the islets of Langerhans in the rat. Diabetes31:883-889.
9. D.BoscoM.ArmanetP.MorelN.NiclaussA.SgroiY.D.MullerL.GiovannoniG.ParnaudT.Berney (2010). Unique arrangement of alpha- and beta-cells in human islets of Langerhans. Diabetes59:1202-1210.
10. M.Braun (2014). The somatostatin receptor in human pancreatic beta-cells. Vitam Horm95:165-193.
11. M.BraunR.RamracheyaS.AmistenM.BengtssonY.MoritohQ.ZhangP.R.JohnsonP.Rorsman (2009). Somatostatin release, electrical activity, membrane currents and exocytosis in human pancreatic delta cells. Diabetologia52:1566-1578.
12. P.BrazeauW.ValeR.BurgusN.LingM.ButcherJ.RivierR.Guillemin (1973). Hypothalamic polypeptide that inhibits the secretion of immunoreactive pituitary growth hormone. Science179:77-79.
13. M.F.BreretonM.IberlK.ShimomuraQ.ZhangA.E.AdriaenssensP.ProksI.I.SpiliotisW.DaceK.K.MattisR.RamracheyaF.M.GribbleF.ReimannA.ClarkP.RorsmanF.M.Ashcroft (2014). Reversible changes in pancreatic islet structure and function produced by elevated blood glucose. Nat Commun5:4639.
14. F.C.BrunicardiJ.StagnerS.Bonner-WeirH.WaylandR.KleinmanE.LivingstonP.GuthM.MengerR.McCuskeyM.IntagliettaA.CharlesS.AshleyA.CheungE.IppS.GilmanT.HowardE.PassaroJr. (1996). Microcirculation of the islets of Langerhans. Long Beach Veterans Administration Regional Medical Education Center Symposium. Diabetes45:385-392.
15. A.E.ButlerJ.JansonS.Bonner-WeirR.RitzelR.A.RizzaP.C.Butler (2003). Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes52:102-110.
16. O.CabreraD.M.BermanN.S.KenyonC.RicordiP.O.BerggrenA.Caicedo (2006). The unique cytoarchitecture of human pancreatic islets has implications for islet cell function. Proc Natl Acad Sci U S A103:2334-2339.
17. A.ClarkM.R.Nilsson (2004). Islet amyloid: a complication of islet dysfunction or an aetiological factor in Type 2 diabetes? Diabetologia47:157-169.
18. A.ClarkC.A.WellsI.D.BuleyJ.K.CruickshankR.I.VanheganD.R.MatthewsG.J.CooperR.R.HolmanR.C.Turner (1988). Islet amyloid, increased A-cells, reduced B-cells and exocrine fibrosis: quantitative changes in the pancreas in type 2 diabetes. Diabetes Res9:151-159.
19. P.CollombatX.XuP.RavassardB.Sosa-PinedaS.DussaudN.BillestrupO.D.MadsenP.SerupH.HeimbergA.Mansouri (2009). The ectopic expression of Pax4 in the mouse pancreas converts progenitor cells into alpha and subsequently beta cells. Cell138:449-462.
20. S.L.ConarelloG.JiangJ.MuZ.LiJ.WoodsE.ZycbandJ.RonanF.LiuR.S.RoyL.ZhuM.J.CharronB.B.Zhang (2007). Glucagon receptor knockout mice are resistant to diet-induced obesity and streptozotocin-mediated beta cell loss and hyperglycaemia. Diabetologia50:142-150.
21. M.CourtneyE.GjernesN.DruelleC.RavaudA.VieiraN.Ben-OthmanA.PfeiferF.AvolioG.LeuckxS.Lacas-GervaisF.Burel-VandenbosD.AmbrosettiJ.Hecksher-SorensenP.RavassardH.HeimbergA.MansouriP.Collombat (2013). The inactivation of Arx in pancreatic alpha-cells triggers their neogenesis and conversion into functional beta-like cells. PLoS Genet9:e1003934.
22. P.E.Cryer (2002). The pathophysiology of hypoglycaemia in diabetes. Diabetes Nutr Metab15:330-333; discussion 362.
23. R.R.De KrijgerH.J.AanstootG.KranenburgM.ReinhardW.J.VisserG.J.Bruining (1992). The midgestational human fetal pancreas contains cells coexpressing islet hormones. Dev Biol153:368-375.
24. Y.Z.De MarinisA.SalehiC.E.WardQ.ZhangF.AbdulkaderM.BengtssonO.BrahaM.BraunR.RamracheyaS.AmistenA.M.HabibY.MoritohE.ZhangF.ReimannA.H.RosengrenT.ShibasakiF.GribbleE.RenstromS.SeinoL.EliassonP.Rorsman (2010). GLP-1 inhibits and adrenaline stimulates glucagon release by differential modulation of N- and L-type Ca2+ channel-dependent exocytosis. Cell Metab11:543-553.
25. J.F.DeconinckP.R.PotvliegeW.Gepts (1971). The ultrastruture of the human pancreatic islets. I. The islets of adults. Diabetologia7:266-282.
26. B.E.DunningJ.E.Gerich (2007). The role of alpha-cell dysregulation in fasting and postprandial hyperglycemia in type 2 diabetes and therapeutic implications. Endocr Rev28:253-283.
27. J.L.DunphyR.G.TaylorP.J.Fuller (1998). Tissue distribution of rat glucagon receptor and GLP-1 receptor gene expression. Mol Cell Endocrinol141:179-186.
28. A.A.ElayatM.M.el-NaggarM.Tahir (1995). An immunocytochemical and morphometric study of the rat pancreatic islets. J Anat186 (Pt 3): 629-637.
29. S.FalkmerY.Ostberg (1977). Comparative morphology of pancreatic islet in animals. In: B.W.VolkK.F.Wellman, eds. The diabetic pancreas. Macmillan, London, pp 15-59.
30. A.FernandesL.C.KingY.GuzR.SteinC.V.WrightG.Teitelman (1997). Differentiation of new insulin-producing cells is induced by injury in adult pancreatic islets. Endocrinology138:1750-1762.
31. B.C.FieldO.B.ChaudhriS.R.Bloom (2010). Bowels control brain: gut hormones and obesity. Nat Rev Endocrinol6:444-453.
32. A.K.FoulisM.McGillM.A.Farquharson (1991). Insulitis in type 1 (insulin-dependent) diabetes mellitus in man–macrophages, lymphocytes, and interferon-gamma containing cells. J Pathol165:97-103.
33. A.K.FoulisJ.A.Stewart (1984). The pancreas in recent-onset type 1 (insulin-dependent) diabetes mellitus: insulin content of islets, insulitis and associated changes in the exocrine acinar tissue. Diabetologia26:456-461.
34. B.H.FrancisD.G.BaskinD.R.SaundersJ.W.Ensinck (1990). Distribution of somatostatin-14 and somatostatin-28 gastrointestinal-pancreatic cells of rats and humans. Gastroenterology99:1283-1291.
35. M.FurutaH.YanoA.ZhouY.RouilleJ.J.HolstR.CarrollM.RavazzolaL.OrciH.FurutaD.F.Steiner (1997). Defective prohormone processing and altered pancreatic islet morphology in mice lacking active SPC2. Proc Natl Acad Sci U S A94:6646-6651.
36. M.FurutaA.ZhouG.WebbR.CarrollM.RavazzolaL.OrciD.F.Steiner (2001). Severe defect in proglucagon processing in islet A-cells of prohormone convertase 2 null mice. J Biol Chem276:27197-27202.
37. T.GaoB.McKennaC.LiM.ReichertJ.NguyenT.SinghC.YangA.PannikarN.DolibaT.ZhangD.A.StoffersH.EdlundF.MatschinskyR.SteinB.Z.Stanger (2014). Pdx1 Maintains beta Cell Identity and Function by Repressing an alpha Cell Program. Cell Metab19:259-271.
38. W.GeptsJ.De MeyM.Marichal-Pipeleers (1977). Hyperplasia of “pancreatic polypeptide”-cells in the pancreas of juvenile diabetics. Diabetologia13:27-34.
39. S.GopelQ.ZhangL.EliassonX.S.MaJ.GalvanovskisT.KannoA.SalehiP.Rorsman (2004). Capacitance measurements of exocytosis in mouse pancreatic alpha-, beta- and delta-cells within intact islets of Langerhans. J Physiol556:711-726.
40. V.GrillS.Efendić (1984). Stimulation by calcium and barium of somatostatin release. Evidence for lower sensitivity of D- vis-à-vis B- and A-cells. Acta Physiol Scand122:401-407.
41. J.GromadaI.FranklinC.B.Wollheim (2007). Alpha-cells of the endocrine pancreas: 35 years of research but the enigma remains. Endocr Rev28:84-116.
42. J.GromadaJ.J.HolstP.Rorsman (1998). Cellular regulation of islet hormone secretion by the incretin hormone glucagon-like peptide 1. Pflügers Archiv435:583-594.
43. J.GromadaM.HøyK.BuschardA.SalehiP.Rorsman (2001). Somatostatin inhibits exocytosis in rat pancreatic alpha-cells by G(i2)-dependent activation of calcineurin and depriming of secretory granules. J Physiol535:519-532.
44. D.GrubeR.Bohn (1983). The microanatomy of human islets of Langerhans, with special reference to somatostatin (D-) cells. Arch Histol Jpn46:327-353.
45. P.C.GuestS.M.Abdel-HalimD.J.GrossA.ClarkV.PoitoutR.AmariaC.G.OstensonJ.C.Hutton (2002). Proinsulin processing in the diabetic Goto-Kakizaki rat. J Endocrinol175:637-647.
46. E.GylfeP.Gilon (2014). Glucose regulation of glucagon secretion. Diabetes Res Clin Pract103:1-10.
47. A.C.Hauge-EvansA.J.KingD.CarmignacC.C.RichardsonI.C.RobinsonM.J.LowM.R.ChristieS.J.PersaudP.M.Jones (2009). Somatostatin secreted by islet delta-cells fulfills multiple roles as a paracrine regulator of islet function. Diabetes58:403-411.
48. P.J.HavelG.J.TaborskyJr. (1989). The contribution of the autonomic nervous system to changes of glucagon and insulin secretion during hypoglycemic stress. Endocr Rev10:332-350.
49. B.HellmanA.WallgrenC.Hellerstrom (1962). Two types of islet alpha cells in different parts of the pancreas of the dog. Nature194:1201-1202.
50. J.C.HenquinJ.Rahier (2011). Pancreatic alpha cell mass in European subjects with type 2 diabetes. Diabetologia54:1720-1725.
51. T.HökfeltS.EfendićC.HellerströmO.JohanssonR.LuftA.Arimura (1975). Cellular localization of somatostatin in endocrine-like cells and neurons of the rat with special references to the A1-cells of the pancreatic islets and to the hypothalamus. Acta Endocrinol Suppl (Copenh)200:5-41.
52. P.HolzerF.ReichmannA.Farzi (2012). Neuropeptide Y, peptide YY and pancreatic polypeptide in the gut-brain axis. Neuropeptides46:261-274.
53. K.IkiP.M.Pour (2007). Distribution of pancreatic endocrine cells including IAPP-expressing cells in non-diabetic and type 2 diabetic cases. J Histochem Cytochem55:111-118.
54. E.IppJ.RivierR.E.DobbsM.BrownW.ValeR.H.Unger (1979). Somatostatin analogs inhibit somatostatin release. Endocrinology104:1270-1273.
55. G.JiangB.B.Zhang (2003). Glucagon and regulation of glucose metabolism. Am J Physiol Endocrinol Metab284:E671-678.
56. X.JingD.Q.LiC.S.OlofssonA.SalehiV.V.SurveJ.CaballeroR.IvarssonI.LundquistA.PereverzevT.SchneiderP.RorsmanE.Renstrom (2005). CaV2.3 calcium channels control second-phase insulin release. J Clin Invest115:146-154.
57. C.A.JurgensM.N.ToukatlyC.L.FlignerJ.UdayasankarS.L.SubramanianS.ZraikaK.Aston-MourneyD.B.CarrP.WestermarkG.T.WestermarkS.E.KahnR.L.Hull (2011). beta-cell loss and beta-cell apoptosis in human type 2 diabetes are related to islet amyloid deposition. Am J Pathol178:2632-2640.
58. B.KaileyD.vandeM.BuntS.CheleyP.R.JohnsonP.E.MacDonaldA.L.GloynP.RorsmanM.Braun (2012). SSTR2 is the functionally dominant somatostatin receptor in human pancreatic beta- and alpha-cells. Am J Physiol Endocrinol Metab303:E1107-1116.
59. T.KannoS.O.GopelP.RorsmanM.Wakui (2002). Cellular function in multicellular system for hormone-secretion: electrophysiological aspect of studies on alpha-, beta- and delta-cells of the pancreatic islet. Neurosci Res42:79-90.
60. T.J.KiefferJ.F.Habener (1999). The glucagon-like peptides. Endocr Rev20:876-913.
61. T.J.KiefferR.S.HellerC.G.UnsonG.C.WeirJ.F.Habener (1996). Distribution of glucagon receptors on hormone-specific endocrine cells of rat pancreatic islets. Endocrinology137:5119-5125.
62. G.KilimnikB.ZhaoJ.JoV.PeriwalP.WitkowskiR.MisawaM.Hara (2011). Altered islet composition and disproportionate loss of large islets in patients with type 2 diabetes. PLoS One6:e27445.
63. J.R.KimmelL.J.HaydenH.G.Pollock (1975). Isolation and characterization of a new pancreatic polypeptide hormone. J Biol Chem250:9369-9376.
64. G.KloppelM.LohrK.HabichM.OberholzerP.U.Heitz (1985). Islet pathology and the pathogenesis of type 1 and type 2 diabetes mellitus revisited. Surv Synth Pathol Res4:110-125.
65. H.J.KreienkampH.H.HönckD.Richter (1997). Coupling of rat somatostatin receptor subtypes to a G-protein gated inwardly rectifying potassium channel (GIRK1). FEBS Lett419:92-94.
66. R.N.KulkarniM.G.RoperG.DahlgrenD.Q.ShihL.M.KauriJ.L.PetersM.StoffelR.T.Kennedy (2004). Islet secretory defect in insulin receptor substrate 1 null mice is linked with reduced calcium signaling and expression of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)-2b and -3. Diabetes53:1517-1525.
67. U.KumarR.SasiS.SureshA.PatelM.ThangarajuP.MetrakosS.C.PatelY.C.Patel (1999). Subtype-selective expression of the five somatostatin receptors (hSSTR1-5)in human pancreatic islet cells: a quantitative double-label immunohistochemical analysis. Diabetes48:77-85.
68. L.I.LarssonF.SundlerR.Hakanson (1975). Immunohistochemical localization of human pancreatic polypeptide (HPP) to a population of islet cells. Cell Tissue Res156:167-171.
69. Y.LeeM.Y.WangX.Q.DuM.J.CharronR.H.Unger (2011). Glucagon receptor knockout prevents insulin-deficient type 1 diabetes in mice. Diabetes60:391-397.
70. E.H.LeiterD.A.GappJ.J.EppigD.L.Coleman (1979). Ultrastructural and morphometric studies of delta cells in pancreatic islets from C57BL/Ks diabetes mice. Diabetologia17:297-309.
71. T.M.LinR.E.Chance (1974). Candidate hormones of the gut. VI. Bovine pancreatic polypeptide (BPP) and avian pancreatic polypeptide (APP). Gastroenterology67:737-738.
72. T.H.LindsayK.G.HalvorsonC.M.PetersJ.R.GhilardiM.A.KuskowskiG.Y.WongP.W.Mantyh (2006). A quantitative analysis of the sensory and sympathetic innervation of the mouse pancreas. Neuroscience137:1417-1426.
73. Y.M.LiuP.H.GuthK.KanekoE.H.LivingstonF.C.Brunicardi (1993). Dynamic in vivo observation of rat islet microcirculation. Pancreas8:15-21.
74. C.LonguetE.M.SinclairA.MaidaL.L.BaggioM.MaziarzM.J.CharronD.J.Drucker (2008). The glucagon receptor is required for the adaptive metabolic response to fasting. Cell Metab8:359-371.
75. J.T.LowM.ZavortinkJ.M.MitchellW.J.GanO.H.DoC.J.SchwieningH.Y.GaisanoP.Thorn (2014). Insulin secretion from beta cells in intact mouse islets is targeted towards the vasculature. Diabetologia57:1655-1663.
76. N.MacleanR.F.Ogilvie (1955). Quantitative estimation of the pancreatic islet tissue in diabetic subjects. Diabetes4:367-376.
77. P.MarchettiR.LupiM.BuglianiC.L.KirkpatrickG.SebastianiF.A.GriecoS.Del GuerraV.D’AleoS.PiroL.MarselliU.BoggiF.FilipponiL.TintiL.SalviniC.B.WollheimF.PurrelloF.Dotta (2012). A local glucagon-like peptide 1 (GLP-1) system in human pancreatic islets. Diabetologia55:3262-3272.
78. M.MarcinkiewiczD.RamlaN.G.SeidahM.Chrétien (1994). Developmental expression of the prohormone convertases PC1 and PC2 in mouse pancreatic islets. Endocrinology135:1651-1660.
79. J.MolinaR.Rodriguez-DiazA.FachadoM.C.Jacques-SilvaP.O.BerggrenA.Caicedo (2014). Control Of Insulin Secretion By Cholinergic Signaling In The Human Pancreatic Islet. Diabetes
80. W.A.MullerG.R.FaloonaE.Aguilar-ParadaR.H.Unger (1970). Abnormal alpha-cell function in diabetes. Response to carbohydrate and protein ingestion. N Engl J Med283:109-115.
81. W.A.MullerG.R.FaloonaR.H.Unger (1973). Hyperglucagonemia in diabetic ketoacidosis. Its prevalence and significance. Am J Med54:52-57.
82. J.R.MurlinH.D.CloughC.B.F.GibbsA.M.Stokes (1923). Aqueous extracts of pancreas: I. Influence on the carbohydrate metabolism of depancreatized animals. J Biol Chem56:253-296.
83. L.R.NymanK.S.WellsW.S.HeadM.McCaugheyE.FordM.BrissovaD.W.PistonA.C.Powers (2008). Real-time, multidimensional in vivo imaging used to investigate blood flow in mouse pancreatic islets. J Clin Invest118:3790-3797.
84. O.OhtaniT.UshikiH.KanazawaT.Fujita (1986). Microcirculation of the pancreas in the rat and rabbit with special reference to the insulo-acinar portal system and emissary vein of the islet. Arch Histol Jpn49:45-60.
85. E.L.Opie (1901). The Relation Oe Diabetes Mellitus to Lesions of the Pancreas. Hyaline Degeneration of the Islands Oe Langerhans. J Exp Med5:527-540.
86. L.OrciR.H.Unger (1975). Functional subdivision of islets of Langerhans and possible role of D cells. Lancet2:1243-1244.
87. Y.C.PatelC.B.Srikant (1997). Somatostatin receptors. Trends Endocrinol Metab8:398-405.
88. C.R.PfeiferA.ShomoronyM.A.AronovaG.ZhangT.CaiH.XuA.L.NotkinsR.D.Leapman (2014). Quantitative analysis of mouse pancreatic islet architecture by serial block-face SEM. J Struct Biol.
89. R.PiranS.H.LeeC.R.LiA.CharbonoL.M.BradleyF.Levine (2014). Pharmacological induction of pancreatic islet cell transdifferentiation: relevance to type I diabetes. Cell Death Dis5:e1357.
90. A.Pocai (2012). Unraveling oxyntomodulin, GLP1’s enigmatic brother. J Endocrinol215:335-346.
91. G.M.Portela-GomesL.GrimeliusP.WestermarkM.Stridsberg (2010). Somatostatin receptor subtypes in human type 2 diabetic islets. Pancreas39:836-842.
92. J.RahierR.M.GoebbelsJ.C.Henquin (1983a). Cellular composition of the human diabetic pancreas. Diabetologia24:366-371.
93. J.RahierJ.WallonS.LoozenA.LefevreW.GeptsJ.Haot (1983b). The pancreatic polypeptide cells of the human pancreas: the effects of age and diabetes. J Clinical Endocrinology and Metabolism56:441-444.
94. G.M.ReavenY.D.ChenA.GolayA.L.SwislockiJ.B.Jaspan (1987). Documentation of hyperglucagonemia throughout the day in nonobese and obese patients with noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab64:106-110.
95. E.RenströmW.G.DingK.BokvistP.Rorsman (1996). Neurotransmitter-induced inhibition of exocytosis in insulin-secreting beta cells by activation of calcineurin. Neuron17:513-522.
96. M.J.RiedelA.AsadiR.WangZ.AoG.L.WarnockT.J.Kieffer (2012). Immunohistochemical characterisation of cells co-producing insulin and glucagon in the developing human pancreas. Diabetologia55:372-381.
97. R.Rodriguez-DiazM.H.AbdulredaA.L.FormosoI.GansC.RicordiP.O.BerggrenA.Caicedo (2011a). Innervation patterns of autonomic axons in the human endocrine pancreas. Cell Metab14:45-54.
98. R.Rodriguez-DiazR.DandoM.C.Jacques-SilvaA.FachadoJ.MolinaM.H.AbdulredaC.RicordiS.D.RoperP.O.BerggrenA.Caicedo (2011b). Alpha cells secrete acetylcholine as a non-neuronal paracrine signal priming beta cell function in humans. Nat Med17:888-892.
99. P.RorsmanL.EliassonT.KannoQ.ZhangS.Gopel (2011). Electrophysiology of pancreatic beta-cells in intact mouse islets of Langerhans. Prog Biophys Mol Biol107:224-235.
100. P.RorsmanR.RamracheyaN.J.RorsmanQ.Zhang (2014). ATP-regulated potassium channels and voltage-gated calcium channels in pancreatic alpha and beta cells: similar functions but reciprocal effects on secretion. Diabetologia57:1749-1761.
101. P.RorsmanS.A.SalehiF.AbdulkaderM.BraunP.E.MacDonald (2008). K(ATP)-channels and glucose-regulated glucagon secretion. Trends Endocrinol Metab19:277-284.
102. J.RossiP.SantamakiM.S.AiraksinenK.H.Herzig (2005). Parasympathetic innervation and function of endocrine pancreas requires the glial cell line-derived factor family receptor alpha2 (GFRalpha2). Diabetes54:1324-1330.
103. K.SaitoN.YaginumaT.Takahashi (1979). Differential volumetry of A, B and D cells in the pancreatic islets of diabetic and nondiabetic subjects. Tohoku J Exp Med129:273-283.
104. H.SakurabaH.MizukamiN.YagihashiR.WadaC.HanyuS.Yagihashi (2002). Reduced beta-cell mass and expression of oxidative stress-related DNA damage in the islet of Japanese Type II diabetic patients. Diabetologia45:85-96.
105. A.SalehiE.VieiraE.Gylfe (2006). Paradoxical stimulation of glucagon secretion by high glucose concentrations. Diabetes55:2318-2323.
106. E.SamolsS.Bonner-WeirG.C.Weir (1986). Intra-islet insulin-glucagon-somatostatin relationships. Clinical Endocrinology and Metabolism15:33-58.
107. T.W.Schwartz (1983). Pancreatic polypeptide: a hormone under vagal control. Gastroenterology85:1411-1425.
108. V.SinghC.GrotzingerK.W.NowakS.ZachariasE.GonczG.PlessI.M.SauerI.EichhornB.Pfeiffer-GuglielmiB.HamprechtB.WiedenmannU.PlockingerM.Z.Strowski (2007). Somatostatin receptor subtype-2-deficient mice with diet-induced obesity have hyperglycemia, nonfasting hyperglucagonemia, and decreased hepatic glycogen deposition. Endocrinology148:3887-3899.
109. H.S.SpijkerR.B.RavelliA.M.Mommaas-KienhuisA.A.van ApeldoornM.A.EngelseA.ZaldumbideS.Bonner-WeirT.J.RabelinkR.C.HoebenH.CleversC.L.MummeryF.CarlottiE.J.de Koning (2013). Conversion of mature human beta-cells into glucagon-producing alpha-cells. Diabetes62:2471-2480.
110. Y.StefanS.GrassoA.PerreletL.Orci (1982a). The pancreatic polypeptide-rich lobe of the human pancreas: definitive identification of its derivation from the ventral pancreatic primordium. Diabetologia23:141-142.
111. Y.StefanL.OrciF.Malaisse-LagaeA.PerreletY.PatelR.H.Unger (1982b). Quantitation of endocrine cell content in the pancreas of nondiabetic and diabetic humans. Diabetes31:694-700.
112. D.J.SteinerA.KimK.MillerM.Hara (2010). Pancreatic islet plasticity: interspecies comparison of islet architecture and composition. Islets2:135-145.
113. F.SundlerR.HakansonL.I.Larsson (1977). Ontogeny of rat pancreatic polypeptide (PP) cells. Cell Tissue Res178:303-306.
114. E.W.SutherlandC.de Duve (1948). Origin and Distribution of the hyperglycemic-glycogenolytic factor of the pancreas. J Biol Chem175:663-674.
115. G.J.TaborskyJr.B.AhrenP.J.Havel (1998). Autonomic mediation of glucagon secretion during hypoglycemia: implications for impaired alpha-cell responses in type 1 diabetes. Diabetes47:995-1005.
116. C.TalchaiS.XuanH.V.LinL.SusselD.Accili (2012). Pancreatic beta cell dedifferentiation as a mechanism of diabetic beta cell failure. Cell150:1223-1234.
117. F.ThorelV.NepoteI.AvrilK.KohnoR.DesgrazS.CheraP.L.Herrera (2010). Conversion of adult pancreatic alpha-cells to beta-cells after extreme beta-cell loss. Nature464:1149-1154.
118. R.H.Unger (1985). Glucagon physiology and pathophysiology in the light of new advances. Diabetologia28:574-578.
119. R.H.UngerE.Aguilar-ParadaW.A.MullerA.M.Eisentraut (1970). Studies of pancreatic alpha cell function in normal and diabetic subjects. J Clin Invest49:837-848.
120. R.H.UngerL.Orci (2010). Paracrinology of islets and the paracrinopathy of diabetes. Proc Natl Acad Sci U S A107:16009-16012.
121. R.H.UngerL.Orci (1975). The essential role of glucagon in the pathogenesis of diabetes mellitus. Lancet1:14-16.
122. E.VieiraY.J.LiuE.Gylfe (2004). Involvement of alpha1 and beta-adrenoceptors in adrenaline stimulation of the glucagon-secreting mouse alpha-cell. Naunyn Schmiedebergs Arch Pharmacol369:179-183.
123. E.VieiraA.SalehiE.Gylfe (2007). Glucose inhibits glucagon secretion by a direct effect on mouse pancreatic alpha cells. Diabetologia50:370-379.
124. P.M.VuguinM.J.Charron (2011). Novel insight into glucagon receptor action: lessons from knockout and transgenic mouse models. Diabetes Obes Metab13 Suppl1:144-150.
125. J.N.WalkerP.R.JohnsonM.ShigetoS.J.HughesA.ClarkP.Rorsman (2011a). Glucose-responsive beta cells in islets isolated from a patient with long-standing type 1 diabetes mellitus. Diabetologia54:200-202.
126. J.N.WalkerR.RamracheyaQ.ZhangP.R.JohnsonM.BraunP.Rorsman (2011b). Regulation of glucagon secretion by glucose: paracrine, intrinsic or both?Diabetes Obes Metab13Suppl 1:95-105.
127. X.WangM.C.ZielinskiR.MisawaP.WenT.Y.WangC.Z.WangP.WitkowskiM.Hara (2013). Quantitative analysis of pancreatic polypeptide cell distribution in the human pancreas. PLoS One8:e55501.
128. G.C.WeirE.SamolsS.LooY.C.PatelK.H.Gabbay (1979). Somatostatin and pancreatic polypeptide secretion: effects of glucagon, insulin, and arginine. Diabetes28:35-40.
129. Y.P.YangF.ThorelD.F.BoyerP.L.HerreraC.V.Wright (2011). Context-specific alpha- to-beta-cell reprogramming by forced Pdx1 expression. Genes Dev25:1680-1685.
130. K.H.YoonS.H.KoJ.H.ChoJ.M.LeeY.B.AhnK.H.SongS.J.YooM.I.KangB.Y.ChaK.W.LeeH.Y.SonS.K.KangH.S.KimI.K.LeeS.Bonner-Weir (2003). Selective beta-cell loss and alpha-cell expansion in patients with type 2 diabetes mellitus in Korea. J Clin Endocrinol Metab88:2300-2308.
131. Q.ZhangM.BengtssonC.PartridgeA.SalehiM.BraunR.CoxL.EliassonP.R.JohnsonE.RenströmT.SchneiderP.O.BerggrenS.GöpelF.M.AshcroftP.Rorsman (2007). R-type Ca(2+)-channel-evoked CICR regulates glucose-induced somatostatin secretion. Nat Cell Biol9:453-460.
132. Q.ZhangM.V.ChibalinaM.BengtssonL.N.GroschnerR.RamracheyaN.J.RorsmanV.LeissM.A.NassarA.WellingF.M.GribbleF.ReimannF.HofmannJ.N.WoodF.M.AshcroftP.Rorsman (2014). Na+ current properties in islet alpha- and beta-cells reflect cell-specific Scn3a and Scn9a expression. J Physiol592:4677-4696.
133. Q.ZhangR.RamracheyaC.LahmannA.TarasovM.BengtssonO.BrahaM.BraunM.BreretonS.CollinsJ.GalvanovskisA.GonzalezL.N.GroschnerN.J.RorsmanA.SalehiM.E.TraversJ.N.WalkerA.L.GloynF.GribbleP.R.JohnsonF.ReimannF.M.AshcroftP.Rorsman (2013). Role of KATP channels in glucose-regulated glucagon secretion and impaired counterregulation in type 2 diabetes. Cell Metab18:871-882.