Structural similarities and differences between the human and the mouse pancreas

Islets

Volumn 7, Issue 1, 2015, Pages

  Dolenšek, Jurij ^a   Rupnik, Marjan Slak ^a,b   Stožer, Andraž ^a  

^a UNIVERSITY OF MARIBOR   (Slovenia)

^b MEDICAL UNIVERSITY OF VIENNA   (Austria)

Author keywords

Anatomy; Endocrine; Exocrine; Human pancreas; Innervation; Islet of Langerhans; Mouse pancreas; Structure; Vasculature

Indexed keywords

GLUCAGON; INSULIN; PANCREAS POLYPEPTIDE; SOMATOSTATIN;

ACINAR CELL; BILE DUCT CARCINOMA; CELL VOLUME; CELLULAR DISTRIBUTION; COMPARATIVE ANATOMY; EFFERENT NERVE; ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY; EXOCRINE SECRETION; HUMAN; INNERVATION; LYMPHATIC SYSTEM; MICROSCOPIC ANATOMY; MOUSE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; ONTOGENY; PANCREAS; PANCREAS CANCER; PANCREAS ISLET CELL; PANCREATIC POLYPEPTIDE SECRETING CELL; PANCREATITIS; REVIEW; SUPERIOR MESENTERIC ARTERY; VASCULARIZATION; ANATOMY AND HISTOLOGY; ANIMAL; DISEASE MODEL; METABOLISM; PANCREAS ISLET; PANCREAS ISLET BETA CELL;

ANIMALS; DISEASE MODELS, ANIMAL; HUMANS; INSULIN-SECRETING CELLS; ISLETS OF LANGERHANS; MICE; PANCREAS;

EID: 84944705104     PISSN: 19382014     EISSN: 19382022     Source Type: Journal    
DOI: 10.1080/19382014.2015.1024405     Document Type: Review

References (187)

1. Case RM. Is the rat pancreas an appropriate model of the human pancreas? Pancreatology 2006; 6:180-90; PMID:16534243; http://dx.doi.org/10.1159/ 000091849
2. Levetan CS, Pierce SM. Distinctions between the islets of mice and men: implications for new therapies for type 1 and 2 diabetes. Endocr Pract 2013; 19:301-12; PMID:23186955; http://dx.doi.org/10.4158/ EP12138.RA
3. Grouwels G, Vasylovska S, Olerud J, Leuckx G, Ngamjariyawat A, Yuchi Y, Jansson L, Van de Casteele M, Kozlova EN, Heimberg H. Differentiating neural crest stem cells induce proliferation of cultured rodent islet beta cells. Diabetologia 2012; 55:2016-25; PMID:22618811; http://dx.doi.org/10.1007/ s00125-012-2542-0
4. Rutter GA, Hodson DJ. Minireview: intraislet regulation of insulin secretion in humans. Mol Endocrinol 2013; 27:1984-95; PMID:24243488; http://dx.doi. org/10.1210/me.2013-1278
5. Farnsworth NL, Benninger RKP. New insights into the role of connexins in pancreatic islet function and diabetes. FEBS Letters 2014; 588:1278-87; PMID:24583073; http://dx.doi.org/10.1016/j.febslet. 2014.02.035
6. Heller RS. The Comparative Anatomy of Islets. In: Islam MS, ed. Islets of Langerhans. Berlin: Springer-Verlag Berlin, 2010:21-37
7. Treuting PM, Dintzis S, Liggitt D, Frevert CW. Comparative Anatomy and Histology: A Mouse and Human Atlas. Elsevier Science, 2011
8. Bockman DE. Anatomy of the Pancreas. In: Go VLW, DiMagno EP, Gardner JD, Lebenthal E, Reber HA, Scheele GA, eds. The Pancreas: Biology, Pathobiology, and Disease New York: Raven Press, 1993:1-8
9. Suda K, Nobukawa B, Takase M, Hayashi T. Pancreatic segmentation on an embryological and anatomical basis. J Hepatobiliary Pancreat Surg 2006; 13:146-8; PMID:16547676; http://dx.doi.org/10.1007/s00534-005-1039-3
10. Rahier J, Wallon J, Henquin JC. Cell populations in the endocrine pancreas of human neonates and infants. Diabetologia 1981; 20:540-6; PMID:6116638; http://dx.doi.org/10.1007/ BF00252762
11. Rahier J, Goebbels RM, Henquin JC. Cellular composition of the human diabetic pancreas. Diabetologia 1983; 24:366-71; PMID:6347784; http://dx.doi.org/ 10.1007/BF00251826
12. Ogilvie RF. A quantitative estimation of the pancreatic islet tissue. QJM 1937; 6:287-300
13. In’t Veld P, Marichal M. Microscopic Anatomy of the Human Islet of Langerhans. The Islets of Langerhans. In: Islam MS, ed.: Springer Netherlands, 2010:1-19
14. Yaginuma N, Takahashi T, Saito K, Kyoguku M. The microvasculature of the human pancreas and its relation to Langerhans islets and lobules. Pathol Res Pract 1986; 181:77-84; PMID:3517840; http://dx.doi.org/ 10.1016/S0344-0338(86)80191-1
15. Rahier J, Wallon J, Henquin JC. Abundance of somatostatin cells in the human neonatal pancreas. Diabetologia 1980; 18:251-4; PMID:6154624; http://dx.doi.org/10.1007/BF00251925
16. Bunnag SC, Bunnag S, Warner NE. Microcirculation in the islets of Langerhans of the mouse. Anat Rec 1963; 146:117-23; PMID:14016852; http://dx.doi. org/10.1002/ar.1091460205
17. Liu XY, Xue LA, Zheng XA, Yan S, Zheng SS. Pancreas transplantation in the mouse. Hepatob Pancreatic Dis Int 2010; 9:254-8
18. Watanabe S, Abe K, Anbo Y, Katoh H. Changes in the mouse exocrine pancreas after pancreatic duct ligation - a qualitative and quantitative histological study. Arch Histol Cytol 1995; 58:365-74; PMID:8527243; http://dx.doi.org/10.1679/aohc.58.365
19. Böck P, Abdel-Moneim M, Egerbacher M. Development of pancreas. Microsc Res Tech 1997; 37:374-83; PMID:9220417; http://dx.doi.org/10.1002/(SICI)1097-0029(19970601)37:5/6%3c374::AID-JEMT2 %3e3.3.CO; 2-R
20. Villasenor A, Chong DC, Henkemeyer M, Cleaver O. Epithelial dynamics of pancreatic branching morphogenesis. Development 2010; 137:4295-305; PMID:21098570; http://dx.doi.org/10.1242/dev. 052993
21. Hörnblad A, Cheddad A, Ahlgren U. An improved protocol for optical projection tomography imaging reveals lobular heterogeneities in pancreatic islet and beta-cell mass distribution. Islets 2011; 3:204-8; PMID:21633198; http://dx.doi.org/10.4161/isl. 3.4.16417
22. Nagai H. Configurational anatomy of the pancreas: its surgical relevance from ontogenetic and comparativeanatomical viewpoints. J Hepatobiliary Pancreat Surg 2003; 10:48-56; PMID:12918457
23. Hörnblad A, Eriksson AU, Sock E, Hill RE, Ahlgren U. Impaired spleen formation perturbs morphogenesis of the gastric lobe of the pancreas. PLoS ONE 2011; 6:e21753; PMID:21738788; http://dx.doi.org/ 10.1371/journal.pone.0021753
24. Saito K, Iwama N, Takahashi T. Morphometrical analysis on topographical difference in size distribution, number and volume of islets in the human pancreas. Tohoku J Exp Med 1978; 124:177-86; PMID:347635; http:// dx.doi.org/10.1620/tjem.124.177
25. Murakami T, Hitomi S, Ohtsuka A, Taguchi T, Fujita T. Pancreatic insulo-acinar portal systems in humans, rats, and some other mammals: Scanning electron microscopy of vascular casts. Microsc Res Tech 1997; 37:478-88; PMID:9220425; http://dx. doi.org/10.1002/(SICI)1097-0029(19970601)37:5/ 6%3c478::AID-JEMT10%3e3.0.CO; 2-N
26. Murakami T, Fujita T, Miyake T, Ohtsuka A, Taguchi T, Kikuta A. The insulo-acinar portal and insulovenous drainage systems in the pancreas of the mouse, dog, monkey, and certain other animals - a scanning electron-microscopic study of corrosion casts. Arch Histol Cytol 1993; 56:127-47; PMID:8373657; http://dx.doi.org/10.1679/aohc.56.127
27. Watanabe T, Yaegashi H, Koizumi M, Toyota T, Takahashi T. The lobular architecture of the normal human pancreas: a computer-assisted three-dimensional reconstruction study. Pancreas 1997; 15:48-52; PMID:9211492; http://dx.doi.org/10.1097/ 00006676-199707000-00007
28. Tadokoro H, Takase M, Nobukawa B. Development and congenital anomalies of the pancreas. Anatomy Res Int 2011; 2011: 1-7.
29. Reichert M, Rustgi AK. Pancreatic ductal cells in development, regeneration, and neoplasia. J Clin Invest 2011; 121:4572-8; PMID:22133881; http:// dx.doi.org/10.1172/JCI57131
30. Tadokoro H, Takase M, Nobukawa B. Unusual fusion between ventral and dorsal primordia causes anomalous pancreaticobiliary junction. Pathol Int 2008; 58:498-502; PMID:18705770; http://dx.doi. org/10.1111/j.1440-1827.2008.02263.x
31. Lacy PE, Kostianovsky M. Method for the isolation of intact islets of Langerhans from the rat pancreas. Diabetes 1967; 16:35-9; PMID:5333500; http://dx.doi. org/10.2337/diab.16.1.35
32. Speier S, Rupnik M. A novel approach to in situ characterization of pancreatic ß-cells. Pflügers Archiv 2003; 446:553-8; PMID:12774232; http://dx.doi. org/10.1007/s00424-003-1097-9
33. Stožer A, Dolenšek J, Rupnik MS. Glucose-Stimulated Calcium Dynamics in Islets of Langerhans in Acute Mouse Pancreas Tissue Slices. PLoS One 2013; 8:e54638; http://dx.doi.org/10.1371/journal.pone. 0054638
34. Skelin Klemen M, Dolenšek J, Stožer A, Rupnik M. Measuring Exocytosis in Endocrine Tissue Slices. In: Thorn P, ed. Exocytosis Methods: Humana Press, 2014:127-46
35. Ricordi C, Lacy PE, Finke EH, Olack BJ, Scharp DW. Automated method for isolation of human pancreatic islets. Diabetes 1988; 37:413-20; PMID:3288530; http://dx.doi.org/10.2337/diab.37.4.413
36. Marciniak A, Cohrs CM, Tsata V, Chouinard JA, Selck C, Stertmann J, Reichelt S, Rose T, Ehehalt F, Weitz J, et al. Using pancreas tissue slices for in situ studies of islet of Langerhans and acinar cell biology. Nat Protoc 2014; 9:2809-22; PMID:25393778; http://dx.doi.org/10.1038/nprot.2014.195
37. Opie EL, Meakins JC. Data concerning the etiology and pathology of hemorrhagic necrosis of the pancreas (acute hemorrhagic pancreatitis). J Exp Med 1909; 11:561-78; PMID:19867267; http://dx.doi.org/ 10.1084/jem.11.4.561
38. Löhr JM, Schneider A, Diehl SJ, Witt H. Opie’s hypothesis revisited: Acute pancreatitis due to bile reflux into the pancreas. Pancreatology 2012; 12:39-40; PMID:22487472; http://dx.doi.org/10.1016/j. pan.2011.12.001
39. Langerhans P. Beiträge zur mikroskopischen Anatomie der Bauchspeicheldrüse: Inaugural-Dissertation. Berlin: Lange, 1869
40. Bouwens L, Pipeleers DG. Extra-insular beta cells associated with ductules are frequent in adult human pancreas. Diabetologia 1998; 41:629-33; PMID:9662042; http:// dx.doi.org/10.1007/s001250050960
41. Merkwitz C, Blaschuk OW, Schulz A, Lochhead P, Meister J, Ehrlich A, Ricken AM. The ductal origin of structural and functional heterogeneity between pancreatic islets. Prog Histochem Cytochem 2013; 48:103-40; PMID:24100070; http://dx.doi.org/ 10.1016/j.proghi.2013.09.001
42. Rupnik M. The physiology of rodent beta-cells in pancreas slices. Acta Physiologica 2009; 195:123-38; PMID:18983446; http://dx.doi.org/10.1111/j.1748-1716.2008.01927.x
43. Hellman B. Actual distribution of the number and volume of the islets of langerhans in different size classes in non-diabetic humans of varying ages. Nature 1959; 184:1498-9; PMID:14400897; http://dx.doi. org/10.1038/1841498a0
44. Kim A, Miller K, Jo J, Kilimnik G, Wojcik P, Hara M. Islet architecture: A comparative study. Islets 2009; 1:129-36; PMID:20606719; http://dx.doi.org/ 10.4161/isl.1.2.9480
45. Kilimnik G, Jo J, Periwal V, Zielinski MC, Hara M. Quantification of islet size and architecture. Islets 2012; 4:167-72; PMID:22653677; http://dx.doi.org/ 10.4161/isl.19256
46. Jo J, Choi MY, Koh D-S. Size distribution of mouse langerhans islets. Biophys J 2007; 93:2655-66; PMID:17586568; http://dx.doi.org/10.1529/ biophysj.107.104125
47. Steiner DJ, Kim A, Miller K, Hara M. Pancreatic islet plasticity Interspecies comparison of islet architecture and composition. Islets 2010; 2:135-45; PMID:20657742; http://dx.doi.org/10.4161/isl.2.3.11815
48. Brissova M, Fowler MJ, Nicholson WE, Chu A, Hirshberg B, Harlan DM, Powers AC. Assessment of human pancreatic islet architecture and composition by laser scanning confocal microscopy. J Histochem Cytochem 2005; 53:1087-97; PMID:15923354; http://dx.doi.org/10.1369/jhc.5C6684.2005
49. Cabrera O, Berman DM, Kenyon NS, Ricordi C, Berggren P-O, Caicedo A. The unique cytoarchitecture of human pancreatic islets has implications for islet cell function. Proc Natl Acad Sci U S A 2006; 103:2334-9; PMID:16461897; http://dx.doi.org/ 10.1073/pnas.0510790103
50. Rahier J, Wallon J, Gepts W, Haot J. Localization of pancreatic polypeptide cells in a limited lobe of the human neonate pancreas: remnant of the ventral primordium? Cell Tissue Res 1979; 200:359-66; PMID:487404; http://dx.doi.org/10.1007/ BF00234848
51. Stefan Y, Grasso S, Perelet A, Orci L. The pancreatic polypeptide-rich lobe of the human pancreas: Definitive identification of its derivation from the ventral pancreatic primordium. Diabetologia 1982; 23:141-2; PMID:7128966; http://dx.doi.org/10.1007/ BF01271177
52. Andralojc KM, Mercalli A, Nowak KW, Albarello L, Calcagno R, Luzi L, Bonifacio E, Doglioni C, Piemonti L. Ghrelin-producing epsilon cells in the developing and adult human pancreas. Diabetologia 2009; 52:486-93; PMID:19096824; http://dx.doi.org/ 10.1007/s00125-008-1238-y
53. Orci L, Unger RH. Functional Subdivision of Islets of Langerhans and Possible Role of D Cells. Lancet 1975; 2:1243-4; PMID:53729; http://dx.doi.org/ 10.1016/S0140-6736(75)92078-4
54. Ku SK, Lee HS, Lee JH. An immunohistochemical study on the pancreatic endocrine cells of the C57BL/ 6 mouse. J Vet Sci 2002; 3:327-33; PMID:12819383
55. Pfeifer CR, Shomorony A, Aronova MA, Zhang G, Cai T, Xu H, Notkins AL, Leapman RD. Quantitative analysis of mouse pancreatic islet architecture by serial block-face SEM. J Struct Biol 2015; 189:44-52; PMID:25448885; http://dx.doi.org/10.1016/j. jsb.2014.10.013
56. Erlandsen SL, Hegre OD, Parsons JA, McEvoy RC, Elde RP. Pancreatic islet cell hormones distribution of cell types in the islet and evidence for the presence of somatostatin and gastrin within the D cell. J Histochem Cytochem 1976; 24:883-97; PMID:60437; http://dx.doi.org/10.1177/24.7.60437
57. Grube D, Bohn R. The microanatomy of human islets of Langerhans, with special reference to somatostatin (D-) cells. Arch Histol Jpn 1983; 46:327-53; PMID:6139102
58. Bosco D, Armanet M, Morel P, Niclauss N, Sgroi A, Muller YD, Giovannoni L, Parnaud G, Berney T. Unique arrangement of alpha- and beta-cells in human islets of Langerhans. Diabetes 2010; 59:1202-10; PMID:20185817; http://dx.doi.org/10.2337/ db09-1177
59. Henquin J, Rahier J. Pancreatic alpha cell mass in European subjects with type 2 diabetes. Diabetologia 2011; 54:1720-5; PMID:21465328; http://dx.doi. org/10.1007/s00125-011-2118-4
60. ioscillations in single human pancreatic islets. Cell Calcium 1996; 20:409-14; PMID:8955555; http://dx.doi.org/ 10.1016/S0143-4160(96)90003-2
61. 2+concentration oscillatory patterns in identified alpha- and betacells within intact human islets of Langerhans. Diabetes 2006; 55:2463-9; PMID:16936194; http://dx.doi. org/10.2337/db06-0272
62. Huypens P, Ling Z, Pipeleers D, Schuit F. Glucagon receptors on human islet cells contribute to glucose competence of insulin release. Diabetologia 2000; 43:1012-9; PMID:10990079; http://dx.doi.org/ 10.1007/s001250051484
63. Wojtusciszyn A, Armanet M, Morel P, Berney T, Bosco D. Insulin secretion from human beta cells is heterogeneous and dependent on cell-to-cell contacts. Diabetologia 2008; 51:1843-52; PMID:18665347; http://dx.doi.org/10.1007/s00125-008-1103-z
64. Rorsman P, Braun M. Regulation of insulin secretion in human pancreatic islets. Annu Rev Physiol 2013; 75:155-79; PMID:22974438; http://dx.doi.org/ 10.1146/annurev-physiol-030212-183754
65. Henquin JC, Dufrane D, Nenquin M. Nutrient control of insulin secretion in isolated normal human islets. Diabetes 2006; 55:3470-7; PMID:17130494; http://dx.doi.org/10.2337/db06-0868
66. Kharouta M, Miller K, Kim A, Wojcik P, Kilimnik G, Dey A, Steiner DF, Hara M. No mantle formation in rodent islets-The prototype of islet revisited. Diabetes Res Clin Pract 2009; 85:252-7; PMID:19595468; http://dx.doi.org/10.1016/j.diabres.2009.06.021
67. Jay TR, Heald KA, Carless NJ, Topham DE, Downing R. The distribution of porcine pancreatic betacells at ages 5, 12 and 24 weeks. Xenotransplantation 1999; 6:131-40; PMID:10431790; http://dx.doi.org/ 10.1034/j.1399-3089.1999.00009.x
68. Quay WB. Pancreatic Weight and Histology in the White Whale. J Mammal 1957; 38:185-92; http://dx. doi.org/10.2307/1376308
69. Van Aswegen G, Van Noorden S, Kotze SH, De Vos V, Schoeman JH. The intestine and endocrine pancreas of the African elephant: a histological immunocytochemical and immunofluorescence study. Onderstepoort J Vet Res 1996; 63:335-40; PMID:9173365
70. Michelmore AJ, Keegan DJ, Kramer B. Immunocytochemical identification of endocrine cells in the pancreas of the fruit bat,rousettus aegyptiacus. Gen Comp Endocrinol 1998; 110:319-25; PMID:9593652; http:// dx.doi.org/10.1006/gcen.1998.7077
71. Reddy SN, Bibby NJ, Elliott RB.Cellular distribution of insulin, glucagon, pancreatic polypeptide hormone and somatostatin in the fetal and adult pancreas of the guinea pig: a comparative immunohistochemical study. Eur J Cell Biol 1985; 38:301-5;PMID:2864246
72. Kilimnik G, Zhao B, Jo J, Periwal V, Witkowski P, Misawa R, Hara M. Altered islet composition and disproportionate loss of large islets in patients with type 2 diabetes. PLoS One 2011; 6:e27445; PMID:22102895; http://dx.doi.org/10.1371/journal. pone.0027445
73. Wang X, Misawa R, Zielinski MC, Cowen P, Jo J, Periwal V, Ricordi C, Khan A, Szust J, Shen J, et al. Regional differences in islet distribution in the human pancreas - preferential beta-cell loss in the head region in patients with type 2 diabetes. PLoS One 2013; 8: e67454; PMID:23826303; http://dx.doi.org/ 10.1371/journal.pone.0067454
74. Takei S, Teruya M, Grunewald A, Garcia R, Chan EK, Charles MA. Isolation and function of human and pig islets. Pancreas 1994; 9:150-6; PMID:8190716; http://dx.doi.org/10.1097/ 00006676-199403000-00002
75. Kenmochi T, Miyamoto M, Une S, Nakagawa Y, Moldovan S, Navarro RA, Benhamou PY, Brunicardi FC, Mullen Y. Improved quality and yield of islets isolated from human pancreata using a two-step digestion method. Pancreas 2000; 20:184-90; PMID:10707935; http://dx.doi.org/10.1097/ 00006676-200003000-00012
76. Schmidt-Nielsen K. Scaling, why is Animal Size So Important? Cambridge: Cambridge University Press, 1984
77. Murakami T, Fujita T, Taguchi T, Nonaka Y, Orita K. The blood vascular bed of the human pancreas, with special reference to the insulacinar portal system - scanning electron-microscopy of corrosion casts. Arch Histol Cytol 1992; 55:381-95; PMID:1482603; http://dx.doi.org/10.1679/aohc.55.381
78. Jo J, Kilimnik G, Kim A, Guo C, Periwal V, Hara M. Formation of pancreatic islets involves coordinated expansion of small islets and fission of large interconnected islet-like structures. Biophys J 2011; 101:565-74; PMID:21806924; http://dx.doi.org/10.1016/j. bpj.2011.06.042
79. Bouwens L, Rooman I. Regulation of pancreatic betacell mass. Physiol Rev 2005; 85:1255-70; PMID:16183912; http://dx.doi.org/10.1152/physrev. 00025.2004
80. Montanya E, Nacher V, Biarnés M, Soler J. Linear correlation between beta-cell mass and body weight throughout the lifespan in Lewis rats: role of beta-cell hyperplasia and hypertrophy. Diabetes 2000; 49:1341-6; PMID:10923635; http://dx.doi.org/ 10.2337/diabetes.49.8.1341
81. Bock T, Pakkenberg B, Buschard K. Increased islet volume but unchanged islet number in ob/ob mice. Diabetes 2003; 52:1716-22; PMID:12829638; http://dx.doi.org/10.2337/diabetes.52.7.1716
82. El-Gohary Y, Sims-Lucas S, Lath N, Tulachan S, Guo P, Xiao X, Welsh C, Paredes J, Wiersch J, Prasadan K, et al. Three-dimensional analysis of the islet vasculature. Anat Rec (Hoboken) 2012; 295:1473-81; http://dx.doi.org/10.1002/ar.22530
83. Rahier J, Guiot Y, Goebbels RM, Sempoux C, Henquin JC. Pancreatic beta-cell mass in European subjects with type 2 diabetes. Diabetes Obes Metab 2008; 10:32-42; http://dx.doi.org/10.1111/j.1463-1326.2008.00969.x
84. Saisho Y, Butler AE, Manesso E, Elashoff D, Rizza RA, Butler PC. beta-cell mass and turnover in humans: effects of obesity and aging. Diabetes Care 2013; 36:111-7; PMID:22875233; http://dx.doi.org/ 10.2337/dc12-0421
85. Rankin MM, Kushner JA. Adaptive beta-cell proliferation is severely restricted with advanced age. Diabetes 2009; 58:1365-72; PMID:19265026; http://dx.doi. org/10.2337/db08-1198
86. Meier JJ, Butler AE, Saisho Y, Monchamp T, Galasso R, Bhushan A, Rizza RA, Butler PC. beta-cell replication is the primary mechanism subserving the postnatal expansion of beta-cell mass in humans. Diabetes 2008; 57:1584-94; PMID:18334605; http://dx.doi. org/10.2337/db07-1369
87. Bonner-Weir S. Islet growth and development in the adult. J Mol Endocrinol 2000; 24:297-302; PMID:10828822; http://dx.doi.org/10.1677/jme. 0.0240297
88. Jiang Y, Nishimura W, Devor-Henneman D, Kusewitt D, Wang H, Holloway MP, Dohi T, Sabo E, Robinson ML, Altieri DC, et al. Postnatal expansion of the pancreatic beta-cell mass is dependent on survivin. Diabetes 2008; 57:2718-27; PMID:18599523; http://dx.doi.org/10.2337/db08-0170
89. Liu J, Yu P, Qian W, Li Y, Zhao J, Huan F, Wang J, Xiao H. Perinatal bisphenol A exposure and adult glucose homeostasis: identifying critical windows of exposure. PLoS One 2013; 8:e64143; PMID:23675523; http://dx.doi.org/10.1371/journal. pone.0064143
90. Wu X, Wang L, Schroer S, Choi D, Chen P, Okada H, Woo M. Perinatal survivin is essential for the establishment of pancreatic beta cell mass in mice. Diabetologia 2009; 52:2130-41; PMID:19644667; http://dx.doi.org/10.1007/s00125-009-1469-6
91. Wang X, Zielinski MC, Misawa R, Wen P, Wang TY, Wang C-Z, Witkowski P, Hara M. Quantitative analysis of pancreatic polypeptide cell distribution in the human pancreas. PLoS One 2013; 8:e55501; PMID:23383206; http://dx.doi.org/10.1371/journal. pone.0055501
92. Li D. Diabetes and pancreatic cancer. Mol Carcinog 2012; 51:64-74; PMID:22162232; http://dx.doi.org/ 10.1002/mc.20771
93. Artinyan A, Soriano PA, Prendergast C, Low T, Ellenhorn JDI, Kim J. The anatomic location of pancreatic cancer is a prognostic factor for survival. HPB 2008; 10:371-6; PMID:18982154; http://dx.doi.org/ 10.1080/13651820802291233
94. Raftery A, Chunn J, Gerland P, Ševčǐková H. Bayesian probabilistic projections of life expectancy for all countries. Demography 2013; 50:777-801; PMID:23494599; http://dx.doi.org/10.1007/s13524-012-0193-x
95. Harrison DE, Archer JR. Genetic differences in effects of food restriction on aging in mice. J Nutr 1987; 117:376-82; PMID:3559752
96. Gregg BE, Moore PC, Demozay D, Hall BA, Li M, Husain A, Wright AJ, Atkinson MA, Rhodes CJ. Formation of a human beta-cell population within pancreatic islets is set early in life. J Clin Endocrinol Metab 2012; 97:3197-206; PMID:22745242; http:// dx.doi.org/10.1210/jc.2012-1206
97. Kassem SA, Ariel I, Thornton PS, Scheimberg I, Glaser B. Beta-cell proliferation and apoptosis in the developing normal human pancreas and in hyperinsulinism of infancy. Diabetes 2000; 49:1325-33; PMID:10923633; http://dx.doi.org/10.2337/ diabetes.49.8.1325
98. Georgia S, Bhushan A. beta cell replication is the primary mechanism for maintaining postnatal beta cell mass. J Clin Invest 2004; 114:963-8; PMID:15467835; http:// dx.doi.org/10.1172/JCI200422098
99. Saisho Y, Butler AE, Meier JJ, Monchamp T, Allen-Auerbach M, Rizza RA, Butler PC. Pancreas volumes in humans from birth to age one hundred taking into account sex, obesity, and presence of type-2 diabetes. Clin Anat 2007; 20:933-42; PMID:17879305; http://dx.doi.org/10.1002/ca.20543
100. Proshchina AE, Savel’yev SV. Immunohistochemical Study of alpha- and beta-Cell Distribution in Human Pancreatic Langerhans Islets of Various Types. Bull Exp Biol Med 2013; 155:798-801; PMID:24288769; http://dx.doi.org/10.1007/s10517-013-2255-5
101. Ferner H. Das Inselsystem des pankreas: Entwicklung, Histobiologie und Pathophysiologie mit besonderer Berücksichtigung des Diabetes mellitus. Thieme 1952
102. Robb PM. Development of the islets of Langerhans in man. Nature 1961; 190:1018; PMID:13742049; http://dx.doi.org/10.1038/1901018a0
103. Robb P. The development of the islets of Langerhans in the human foetus. Exp Physiol 1961; 46:335-43; http:// dx.doi.org/10.1113/expphysiol.1961.sp001551
104. Jeon J, Correa-Medina M, Ricordi C, Edlund H, Diez JA. Endocrine cell clustering during human pancreas development. J Histochem Cytochem 2009; 57:811-24; PMID:19365093; http://dx.doi.org/10.1369/ jhc.2009.953307
105. Meier JJ, Köhler CU, Alkhatib B, Sergi C, Junker T, Klein HH, Schmidt WE, Fritsch H. beta-cell development and turnover during prenatal life in humans. Eur J Endocrinol 2010; 162:559-68; PMID:20022941; http://dx.doi.org/10.1530/EJE-09-1053
106. Tschen S-I, Dhawan S, Gurlo T, Bhushan A. Agedependent decline in beta-cell proliferation restricts the capacity of beta-cell regeneration in mice. Diabetes 2009; 58:1312-20; PMID:19228811; http://dx.doi. org/10.2337/db08-1651
107. Sone H, Kagawa Y. Pancreatic beta cell senescence contributes to the pathogenesis of type 2 diabetes in high-fat diet-induced diabetic mice. Diabetologia 2005; 48:58-67; PMID:15624098; http://dx.doi.org/ 10.1007/s00125-004-1605-2
108. Stolovich-Rain M, Hija A, Grimsby J, Glaser B, Dor Y. Pancreatic beta cells in very old mice retain capacity for compensatory proliferation. J Biol Chem 2012; 287:27407-14; PMID:22740691; http://dx.doi.org/ 10.1074/jbc.M112.350736
109. Miller K, Kim A, Kilimnik G, Jo J, Moka U, Periwal V, Hara M. Islet formation during the neonatal development in mice. PLoS One 2009; 4:e7739; PMID:19893748; http://dx.doi.org/10.1371/journal. pone.0007739
110. Teta M, Long SY, Wartschow LM, Rankin MM, Kushner JA. Very slow turnover of beta-cells in aged adult mice. Diabetes 2005; 54:2557-67; PMID:16123343; http://dx.doi.org/10.2337/diabetes.54.9.2557
111. Teta M, Rankin MM, Long SY, Stein GM, Kushner JA. Growth and regeneration of adult beta cells does not involve specialized progenitors. Dev Cell 2007; 12:817-26; PMID:17488631; http://dx.doi.org/ 10.1016/j.devcel.2007.04.011
112. Berglund ED, Li CY, Poffenberger G, Ayala JE, Fueger PT, Willis SE, Jewell MM, Powers AC, Wasserman DH. Glucose metabolism in vivo in four commonly used inbred mouse strains. Diabetes 2008; 57:1790-9; PMID:18398139; http://dx.doi.org/ 10.2337/db07-1615
113. Ku SK, Lee HS, Lee JH. Immunohistochemical study of the pancreatic endocrine cells in the BALB/c mice: an unique distributional pattern of glucagon. J Vet Sci 2002; 3:167-73; PMID:12514327
114. 2+iand Insulin Rhythms in Mouse Islets. PLoS One 2009; 4: e8428; PMID:20037650; http://dx.doi.org/10.1371/ journal.pone.0008428
115. Lewis MP, Reber HA, Ashley SW. Pancreatic blood flow and its role in the pathophysiology of pancreatitis. J Surg Res 1998; 75:81-9; PMID:9614861; http://dx.doi.org/10.1006/jsre.1998.5268
116. Wharton GK. The blood supply of the pancreas, with special reference to that of the islands of Langerhans. Anatomical Record 1932; 53:55-81; http://dx.doi. org/10.1002/ar.1090530108
117. Mikami Y, Otsuka A, Unno M. Surgical Vascular Anatomy and Histology. In: Beger H, Matsuno S, Cameron J, Rau B, Sunamura M, Schulick R, eds. Diseases of the Pancreas: Springer Berlin Heidelberg, 2008:19-28
118. Meyers M, Charnsangavej C, Oliphant M. Patterns of spread of disease from the pancreas. Meyers’ Dynamic Radiology of the Abdomen: Springer New York, 2011:259-74
119. Woodburne RT, Olsen LL. The arteries of the pancreas. Anat Rec 1951; 111:255-70; PMID:14894836; http://dx.doi.org/10.1002/ar.1091110209
120. Bertelli E, Di Gregorio F, Bertelli L, Mosca S. The arterial blood supply of the pancreas: a review. I. The superior pancreaticoduodenal and the anterior superior pancreaticoduodenal arteries. An anatomical and radiological study. Surg Radiol Anat 1995; 17:97-106, 1-3; PMID:7597559; http://dx.doi.org/ 10.1007/BF01627566
121. Bertelli E, Di Gregorio F, Bertelli L, Civeli L, Mosca S. The arterial blood supply of the pancreas: a review. II. The posterior superior pancreaticoduodenal artery. An anatomical and radiological study. Surg Radiol Anat 1996; 18:1-9; PMID:8685804; http://dx.doi. org/10.1007/BF03207753
122. Bertelli E, Di Gregorio F, Bertelli L, Civeli L, Mosca S. The arterial blood supply of the pancreas: a review. III. The inferior pancreaticoduodenal artery. An anatomical review and a radiological study. Surg Radiol Anat 1996; 18:67-74; PMID:8782310; http://dx.doi. org/10.1007/BF01795221
123. Bertelli E, Di Gregorio F, Bertelli L, Orazioli D, Bastianini A. The arterial blood supply of the pancreas: a review: IV. The anterior inferior and posterior pancreaticoduodenal aa., and minor sources of blood supply for the head of the pancreas. An anatomical review and radiologic study. Surg Radiol Anat 1997; 19:203-12; PMID:9381324
124. Bertelli E, Di Gregorio F, Mosca S, Bastianini A. The arterial blood supply of the pancreas: a review. V. The dorsal pancreatic artery. An anatomic review and a radiologic study. Surg Radiol Anat 1999; 20:445-52; http://dx.doi.org/10.1007/s00276-998-0445-z
125. Cook MJ. The anatomy of the laboratory mouse. Academic Press, 1965
126. Love JA, Yi E, Smith TG. Autonomic pathways regulating pancreatic exocrine secretion. Auton Neurosci 2007; 133:19-34; PMID:17113358; http://dx.doi. org/10.1016/j.autneu.2006.10.001
127. Rodriguez-Diaz R, Abdulreda Midhat H, Formoso Alexander L, Gans I, Ricordi C, Berggren P-O, Caicedo A. Innervation Patterns of Autonomic Axons in the Human Endocrine Pancreas. Cell Metab 2011; 14:45-54; PMID:21723503; http://dx.doi.org/ 10.1016/j.cmet.2011.05.008
128. Brunicardi FC, Stagner J, Bonner Weir S, Wayland H, Kleinman R, Livingston E, Guth P, Menger M, McCuskey R, Intaglietta M, et al. Microcirculation of the islets of langerhans - long beach veterans administration regional medical education center symposium. Diabetes 1996; 45:385-92; PMID:8603757; http:// dx.doi.org/10.2337/diab.45.4.385
129. Henderson JR, Daniel PM, Fraser PA. The pancreas as a single organ: the influence of the endocrine upon the exocrine part of the gland. Gut 1981; 22:158-67; PMID:6111521; http://dx.doi.org/10.1136/gut. 22.2.158
130. Henderson JR, Moss MC. A morphometric study of the endocrine and exocrine capillaries of the pancreas. Q J Exp Physiol 1985; 70:347-56; http://dx.doi.org/ 10.1113/expphysiol.1985.sp002920
131. Konstantinova I, Lammert E. Microvascular development: learning from pancreatic islets. BioEssays 2004; 26:1069-75; PMID:15382139; http://dx.doi.org/ 10.1002/bies.20105
132. Saito KEN, Yaginuma N, Takahashi T. Differential volumetry of A, B and D Cells in the pancreatic islets of diabetic and nondiabetic subjects. Tohoku J Exp Med 1979; 129:273-83; PMID:392812; http://dx. doi.org/10.1620/tjem.129.273
133. Nyman LR, Wells KS, Head WS, McCaughey M, Ford E, Brissova M, Piston DW, Powers AC. Realtime, multidimensional in vivo imaging used to investigate blood flow in mouse pancreatic islets. J Clin Invest 2008; 118:3790-7; PMID:18846254; http://dx.doi.org/10.1172/JCI36209
134. Wayland H. Microcirculation in pancreatic function. Microsc Res Tech 1997; 37:418-33; PMID:9220421; http://dx.doi.org/10.1002/(SICI)1097-0029(19970601) 37:5/6%3c418::AID-JEMT6%3e3.0.CO; 2-9
135. Nyman LR, Ford E, Powers AC, Piston DW. Glucose- dependent blood flow dynamics in murine pancreatic islets in vivo. Am J Physiol Endocrinol Metab 2010; 298:E807-E14; PMID:20071562; http://dx. doi.org/10.1152/ajpendo.00715.2009
136. Stagner JI, Samols E. The vascular order of islet cellular perfusion in the human pancreas. Diabetes 1992; 41:93-7; PMID:1345782; http://dx.doi.org/10.2337/ diab.41.1.93
137. Regoli M, Bertelli E, Orazioli D, Fonzi L, Bastianini A. Pancreatic lymphatic system in rodents. Anat Rec 2001; 263:155-60; PMID:11360232; http://dx.doi. org/10.1002/ar.1090
138. O’Morchoe CCC. Lymphatic system of the pancreas. Microsc Res Tech 1997; 37:456-77; PMID:9220424; http://dx.doi.org/10.1002/(SICI)1097-0029(19970601) 37:5/6%3c456::AID-JEMT9%3e3.0.CO; 2-B
139. Navas V, O’Morchoe PJ, O’Morchoe CC. Lymphatic valves of the rat pancreas. Lymphology 1991; 24:146-54; PMID:1791725
140. Henderson JR. Insulin in body fluids other than blood. Physiol Rev 1974; 54:1-22; PMID:4587246
141. Kayahara M, Nagakawa T, Ohta T, Kitagawa H, Ueno K, Tajima H, Elnemr A, Miwa K. Analysis of paraaortic lymph node involvement in pancreatic carcinoma. Cancer 1999; 85:583-90; PMID:10091731; http://dx.doi. org/10.1002/(SICI)1097-0142(19990201) 85:3%3c583::AID-CNCR8%3e3.0.CO; 2-J
142. Kayahara M, Nagakawa T, Kobayashi H, Mori K, Nakano T, Kadoya N, Ohta T, Ueno K, Miyazaki I. Lymphatic flow in carcinoma of the head of the pancreas. Cancer 1992; 70:2061-6; PMID:1327485; http://dx.doi.org/ 10.1002/1097-0142(19921015)70:8%3c2061::AID-CN CR2820700808%3e3.0.CO; 2-V
143. Kayahara M, Nagakawa T, Futagami F, Kitagawa H, Ohta T, Miyazaki I. Lymphatic flow and neural plexus invasion associated with carcinoma of the body and tail of the pancreas. Cancer 1996; 78:2485-91; PMID:8952555; http://dx.doi.org/10.1002/(SICI) 1097-0142(19961215)78:12%3c2485::AID-CNCR 6%3e3.0.CO; 2-J
144. Nagakawa T, Kobayashi H, Ueno K, Ohta T, Kayahara M, Miyazaki I. Clinical study of lymphatic flow to the paraaortic lymph nodes in carcinoma of the head of the pancreas. Cancer 1994; 73:1155-62; PMID:8313317; http://dx.doi.org/10.1002/1097-0142(19940215)73:4%3c1155::AID-CNCR282073 0406%3e3.0.CO; 2-H
145. Kitagawa H, Ohta T, Makino I, Tani T, Tajima H, Nakagawara H, Ohnishi I, Takamura H, Kayahara M, Watanabe H, et al. Carcinomas of the ventral and dorsal pancreas exhibit different patterns of lymphatic spread. Front Biosci 2008; 13:2728-35; PMID:17981748; http://dx.doi.org/10.2741/2880
146. Ahrén B. Autonomic regulation of islet hormone secretion - Implications for health and disease. Diabetologia 2000; 43:393-410; http://dx.doi.org/10.1007/ s001250051322
147. Gilon P, Henquin J-C. Mechanisms and physiological significance of the cholinergic control of pancreatic beta-cell function. Endocr Rev 2001; 22:565-604; PMID:11588141
148. Rodriguez-Diaz R, Caicedo A. Novel approaches to studying the role of innervation in the biology of pancreatic islets. Endocrinol Metab Clin North Am 2013; 42:39-56; PMID:23391238; http://dx.doi.org/ 10.1016/j.ecl.2012.11.001
149. Lindsay TH, Halvorson KG, Peters CM, Ghilardi JR, Kuskowski MA, Wong GY, Mantyh PW. A quantitative analysis of the sensory and sympathetic innervation of the mouse pancreas. Neuroscience 2006; 137:1417-26; PMID:16388907; http://dx.doi.org/ 10.1016/j.neuroscience.2005.10.055
150. Ushiki T, Watanabe S. Distribution and ultrastructure of the autonomic nerves in the mouse pancreas.Microsc Res Tech 1997; 37:399-406; PMID:9220419; http:// dx.doi.org/10.1002/(SICI)1097-0029(19970601)37:5/ 6%3c399::AID-JEMT4%3e3.0.CO; 2-9
151. Havel PJ, Ahren B. Activation of autonomic nerves and the adrenal medulla contributes to increased glucagon secretion during moderate insulininduced hypoglycemia in women. Diabetes 1997; 46:801-7; PMID:9133547; http://dx.doi.org/ 10.2337/diab.46.5.801
152. Teff KL, Mattes RD, Engelman K. Cephalic phase insulin release in normal weight males: verification and reliability. Am J Physiol 1991; 261:E430-6; PMID:1928335
153. Taborsky GJ, Jr., Ahren B, Havel PJ. Autonomic mediation of glucagon secretion during hypoglycemia: implications for impaired alpha-cell responses in type 1 diabetes. Diabetes 1998; 47:995-1005; PMID:9648820; http://dx.doi.org/10.2337/ diabetes.47.7.995
154. Gilliam LK, Palmer JP, Taborsky GJ Jr. Tyraminemediated activation of sympathetic nerves inhibits insulin secretion in humans. J Clin Endocrinol Metab 2007; 92:4035-8; PMID:17684049; http://dx.doi. org/10.1210/jc.2007-0536
155. Dolenšek J, Stožer A, Skelin Klemen M, Miller EW, Slak Rupnik M. The relationship between membrane potential and calcium dynamics in glucose-stimulated beta cell syncytium in acute mouse pancreas tissue slices. PLoS One 2013; 8:e82374; http://dx.doi.org/ 10.1371/journal.pone.0082374
156. Takahashi N, Kishimoto T, Nemoto T, Kadowaki T, Kasai H. Fusion pore dynamics and insulin granule exocytosis in the pancreatic islet. Science 2002; 297:1349-52; PMID:12193788; http://dx.doi.org/ 10.1126/science.1073806
157. Low J, Mitchell J, Do O, Bax J, Rawlings A, Zavortink M, Morgan G, Parton R, Gaisano H, Thorn P. Glucose principally regulates insulin secretion in mouse islets by controlling the numbers of granule fusion events per cell. Diabetologia 2013; 56:2629-37; PMID:23995471; http://dx.doi.org/10.1007/ s00125-013-3019-5
158. Chiu YC, Hua TE, Fu YY, Pasricha PJ, Tang SC. Three-D imaging and illustration of the perfusive mouse islet sympathetic innervation and its remodelling in injury. Diabetologia 2012; 55:3252-61; PMID:22930160; http://dx.doi.org/10.1007/s00125-012-2699-6
159. Rodriguez-Diaz R, Speier S, Molano RD, Formoso A, Gans I, Abdulreda MH, Cabrera O, Molina J, Fachado A, Ricordi C, et al. Noninvasive in vivo model demonstrating the effects of autonomic innervation on pancreatic islet function. Proc Natl Acad Sci 2012; 109:21456-61; http://dx.doi.org/10.1073/ pnas.1211659110
160. Speier S, Nyqvist D, Cabrera O, Yu J, Molano RD, Pileggi A, Moede T, Kohler M, Wilbertz J, Leibiger B, et al. Noninvasive in vivo imaging of pancreatic islet cell biology. Nat Med 2008; 14:574-8; PMID:18327249; http://dx.doi.org/10.1038/nm1701
161. Meneghel-Rozzo T, Rozzo A, Poppi L, Rupnik M. In vivo and in vitro development of mouse pancreatic ß-cells in organotypic slices. Cell Tissue Res 2004; 316:295-303; PMID:15085425; http://dx.doi.org/ 10.1007/s00441-004-0886-6
162. Richins CA. The innervation of the pancreas. J Comp Neurol 1945; 83:223-36; PMID:21009099; http:// dx.doi.org/10.1002/cne.900830303
163. Yi SQ, Miwa K, Ohta T, Kayahara M, Kitagawa H, Tanaka A, Shimokawa T, Akita K, Tanaka S. Innervation of the pancreas from the perspective of perineural invasion of pancreatic cancer. Pancreas 2003; 27:225-9; PMID:14508126; http://dx.doi.org/10.1097/ 00006676-200310000-00005
164. Tiscornia OM. The neural control of exocrine and endocrine pancreas. Am J Gastroenterol 1977; 67:541-60; PMID:20775
165. Honjin R. The innervation of the pancreas of the mouse, with special reference to the structure of the peripheral extension of the vegetative nervous system. J CompNeurol 1956; 104:331-71; PMID:13357632; http://dx.doi. org/10.1002/cne.901040302
166. Su HC, Bishop AE, Power RF, Hamada Y, Polak JM. Dual intrinsic and extrinsic origins of CGRPand NPY-immunoreactive nerves of rat gut and pancreas. J Neurosci 1987; 7:2674-87; PMID:2442325
167. Kayahara M, Nakagawara H, Kitagawa H, Ohta T. The nature of neural invasion by pancreatic cancer. Pancreas 2007; 35:218-23; PMID:17895841; http:// dx.doi.org/10.1097/mpa.0b013e3180619677
168. Makino I, Kitagawa H, Ohta T, Nakagawara H, Tajima H, Ohnishi I, Takamura H, Tani T, Kayahara M. Nerve plexus invasion in pancreatic cancer: spread patterns on histopathologic and embryological analyses. Pancreas 2008; 37:358-65; PMID:18972625; http://dx.doi.org/10.1097/MPA.0b013e31818166e6
169. Ahren B, Veith RC, Taborsky GJ Jr. Sympathetic nerve stimulation versus pancreatic norepinephrine infusion in the dog: 1. Effects on basal release of insulin and glucagon. Endocrinology 1987; 121:323-31; PMID:3297643; http://dx.doi.org/10.1210/endo-121-1-323
170. Dunning BE, Scott MF, Neal DW, Cherrington AD. Direct quantification of norepinephrine spillover and hormone output from the pancreas of the conscious dog. Am J Physiol 1997; 272:E746-55; PMID:9176171
171. Mundinger TO, Verchere CB, Baskin DG, Boyle MR, Kowalyk S, Taborsky GJ, Jr. Galanin is localized in sympathetic neurons of the dog liver. Am J Physiol 1997; 273:E1194-202; PMID:9435536
172. Molina J, Rodriguez-Diaz R, Fachado A, Jacques-Silva MC, Berggren PO, Caicedo A. Control of insulin secretion by cholinergic signaling in the human pancreatic islet. Diabetes 2014; 63:2714-26; PMID:24658304; http://dx.doi.org/10.2337/db13-1371
173. Ahren B, Taborsky GJ Jr. The mechanism of vagal nerve stimulation of glucagon and insulin secretion in the dog. Endocrinology 1986; 118:1551-7; PMID:3512257; http://dx.doi.org/10.1210/endo-118-4-1551
174. Rodriguez-Diaz R, Dando R, Jacques-Silva MC, Fachado A, Molina J, Abdulreda MH, Ricordi C, Roper SD, Berggren PO, Caicedo A. Alpha cells secrete acetylcholine as a non-neuronal paracrine signal priming beta cell function in humans. Nat Med 2011; 17:888-92; PMID:21685896; http://dx.doi. org/10.1038/nm.2371
175. Rodriguez-Diaz R, Menegaz D, Caicedo A. Neurotransmitters act as paracrine signals to regulate insulin secretion from the human pancreatic islet. J Physiol 2014; 592:3413-3417 PMID:24591573
176. Eberhard D, Kragl M, Lammert E. ’Giving and taking’: endothelial and beta-cells in the islets of Langerhans. Trends Endocrinol Metab 2010; 21:457-63; PMID:20359908; http://dx.doi.org/10.1016/j. tem.2010.03.003
177. Eberhard D, Lammert E. The pancreatic beta-cell in the islet and organ community. Curr Opin Genet Dev 2009; 19:469-75; PMID:19713099; http://dx. doi.org/10.1016/j.gde.2009.07.003
178. Kohler CU, Olewinski M, Tannapfel A, Schmidt WE, Fritsch H, Meier JJ. Cell cycle control of beta-cell replication in the prenatal and postnatal human pancreas. Am J Physiol Endocrinol Metab 2011; 300:E221-30; PMID:20978233; http://dx.doi.org/10.1152/ ajpendo.00496.2010
179. Shu L, Zien K, Gutjahr G, Oberholzer J, Pattou F, Kerr-Conte J, Maedler K. TCF7L2 promotes beta cell regeneration in human and mouse pancreas. Diabetologia 2012; 55:3296-307; PMID:22945304; http:// dx.doi.org/10.1007/s00125-012-2693-z
180. Rankin MM, Kushner JA. Aging induces a distinct gene expression program in mouse islets. Islets 2010; 2:345-52; PMID:21099336; http://dx.doi.org/10.4161/isl.2.6.13376
181. Szabat M, Lynn FC, Hoffman BG, Kieffer TJ, Allan DW, Johnson JD. Maintenance of beta-cell maturity and plasticity in the adult pancreas: developmental biology concepts in adult physiology. Diabetes 2012; 61:1365-71; PMID:22618775; http://dx.doi.org/10.2337/db11-1361
182. MacDonald MJ, Longacre MJ, Stoker SW, Kendrick M, Thonpho A, Brown LJ, Hasan NM, Jitrapakdee S, Fukao T, Hanson MS, et al. Differences between Human and Rodent Pancreatic Islets: low pyruvate carboxylase, atp citrate lyase, and pyruvate carboxylation and high glucose-stimulated acetoacetate in human pancreatic islets. J Biol Chem 2011; 286:18383-96; PMID:21454710; http://dx.doi.org/10.1074/jbc.M111.241182
183. Fox JE, Seeberger K, Dai XQ, Lyon J, Spigelman AF, Kolic J, Hajmrle C, Joseph JW, Kin T, Shapiro AM, et al. Functional plasticity of the human infant betacell exocytotic phenotype. Endocrinology 2013; 154:1392-9; PMID:23449893; http://dx.doi.org/10.1210/en.2012-1934
184. Menge BA, Tannapfel A, Belyaev O, Drescher R, Müller C, Uhl W, Schmidt WE, Meier JJ. Partial Pancreatectomy in Adult Humans Does Not Provoke beta-Cell Regeneration. Diabetes 2008; 57:142-9; PMID:17959931; http://dx.doi.org/10.2337/db07-1294
185. Fellmann L, Nascimento AR, Tibirica E, Bousquet P. Murine models for pharmacological studies of the metabolic syndrome. Pharmacol Ther 2013; 137:331-40; PMID:23178510; http://dx.doi.org/10.1016/j. pharmthera.2012.11.004
186. Yip L, Fathman CG. Type 1 diabetes in mice and men: gene expression profiling to investigate disease pathogenesis. Immunol Res 2014; 58:340-50; PMID:24682832; http://dx.doi.org/10.1007/s12026-014-8501-8
187. Chandrasekera PC, Pippin JJ. Of rodents and men: species-specific glucose regulation and type 2 diabetes research. Altex 2014; 31:157-76; PMID:24270692; http://dx.doi.org/10.14573/1309231