Insulin secretion and insulin-producing tumors

Expert Review of Endocrinology and Metabolism

Volumn 5, Issue 2, 2010, Pages 217-227

  Guettier, Jean Marc ^a   Gorden, Phillip ^a  

^a NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES   (United States)

Author keywords

cell; Hypoglycemia; Insulin secretion; Insulinoma; Nesidioblastosis

Indexed keywords

DIAZOXIDE; GLUCOSE; INSULIN; INWARDLY RECTIFYING POTASSIUM CHANNEL SUBUNIT KIR6.2; MONOCARBOXYLATE TRANSPORTER 1; PROINSULIN; SULFONYLUREA RECEPTOR 1;

CELL DAMAGE; CELL DIFFERENTIATION; CELL GROWTH; CELL PROLIFERATION; CLINICAL EVALUATION; CLINICAL FEATURE; DRUG EFFICACY; FAMILIAL DISEASE; GENE DELETION; GENETIC ASSOCIATION; GLUCOSE BLOOD LEVEL; HUMAN; HYPERINSULINISM; HYPOGLYCEMIA; INSULIN BLOOD LEVEL; INSULIN RELEASE; INSULIN SYNTHESIS; INSULINOMA; MOLECULAR DYNAMICS; MULTIPLE ENDOCRINE NEOPLASIA; NONHUMAN; PANCREAS ISLET BETA CELL; PANCREAS ISLET CELL FUNCTION; PANCREAS RESECTION; PATHOGENESIS; PRIORITY JOURNAL; REVIEW; SURVIVAL TIME; TREATMENT RESPONSE; TUMOR LOCALIZATION; TUMOR VOLUME;

EID: 77949639412     PISSN: 17446651     EISSN: None     Source Type: Journal    
DOI: 10.1586/eem.09.83     Document Type: Review

References (120)

1. Gerich JE, Charles MA, Grodsky GM. Characterization of the effects of arginine and glucose on glucagon and insulin release from the perfused rat pancreas. J. Clin. Invest. 54(4), 833-841 (1974
2. Dean PM, Matthews EK. Electrical activity in pancreatic islet cells. Nature 219(5152), 389-390 (1968
3. Dean PM, Matthews EK. Glucose-induced electrical activity in pancreatic islet cells. J. Physiol. 210(2), 255-264 (1970
4. Cook DL, Hales CN. Intracellular ATP directly blocks K+ channels in pancreatic B-cells. Nature 311(5983), 271-273 (1984
5. Ashcroft FM, Harrison DE, Ashcroft SJ. Glucose induces closure of single potassium channels in isolated rat pancreatic b-cells. Nature 312(5993), 446-448 (1984
6. Schwanstecher M, Loser S, Chudziak F, Panten U. Identification of a 38-kDa high affinity sulfonylurea-binding peptide in insulin-secreting cells and cerebral cortex. J. Biol. Chem. 269(27), 17768-17771 (1994
7. Clement JP 4th, Kunjilwar K, Gonzalez G et al. Association and stoichiometry of K(ATP) channel subunits. Neuron 18(5), 827-838 (1997
8. Ohara-Imaizumi M, Nakamichi Y, Nishiwaki C, Nagamatsu S. Transduction of MIN6 b cells with TAT-syntaxin SNARE motif inhibits insulin exocytosis in biphasic insulin release in a distinct mechanism analyzed by evanescent wave microscopy J. Biol. Chem. 277(52), 50805-50811 (2002
9. Ohara-Imaizumi M, Nishiwaki C, Kikuta T, Nagai S, Nakamichi Y, Nagamatsu S. TIRF imaging of docking and fusion of single insulin granule motion in primary rat pancreatic b-cells: different behaviour of granule motion between normal and Goto-Kakizaki diabetic rat b-cells. Biochem. J. 381(Pt 1), 13-18 (2004
10. Pouli AE, Emmanouilidou E, Zhao C, Wasmeier C, Hutton JC, Rutter GA. Secretory-granule dynamics visualized in vivo with a phogrin-green fluorescent protein chimaera. Biochem. J. 333 (Pt 1), 193-199 (1998
11. Varadi A, Ainscow EK, Allan VJ, Rutter GA. Involvement of conventional kinesin in glucose-stimulated secretory granule movements and exocytosis in clonal pancreatic b-cells. J. Cell. Sci. 115(Pt 21), 4177-4189 (2002
12. Henquin JC. Triggering and amplifying pathways of regulation of insulin secretion by glucose. Diabetes 49(11), 1751-1760 (2000
13. Thorens B, Sarkar HK, Kaback HR, Lodish HF. Cloning and functional expression in bacteria of a novel glucose transporter present in liver, intestine, kidney, and b-pancreatic islet cells. Cell 55(2), 281-290 (1988
14. Matschinsky FM. Glucokinase as glucose sensor and metabolic signal generator in pancreatic b-cells and hepatocytes. Diabetes 39(6), 647-652 (1990
15. Barg S, Eliasson L, Renstrom E, Rorsman P. A subset of 50 secretory granules in close contact with L-type Ca2+ channels accounts for first-phase insulin secretion in mouse b-cells. Diabetes 51(Suppl. 1), S74-S82 (2002
16. Dean PM. Ultrastructural morphometry of the pancreatic-cell. Diabetologia 9(2), 115-119 (1973
17. Pedersen MG, Sherman A. Newcomer insulin secretory granules as a highly calcium-sensitive pool. Proc. Natl Acad. Sci. USA 106(18), 7432-7436 (2009
18. Lu D, Mulder H, Zhao P et al. 13C NMR isotopomer analysis reveals a connection between pyruvate cycling and glucose-stimulated insulin secretion (GSIS). Proc. Natl Acad. Sci. USA 99(5), 2708-2713 (2002
19. Maechler P, Wollheim CB. Mitochondrial glutamate acts as a messenger in glucose-induced insulin exocytosis. Nature 402(6762), 685-689 (1999
20. Eto K, Suga S, Wakui M et al. NADH shuttle system regulates K(ATP) channel-dependent pathway and steps distal to cytosolic Ca(2+) concentration elevation in glucose-induced insulin secretion. J. Biol. Chem. 274(36), 25386-25392 (1999
21. Corkey BE, Glennon MC, Chen KS, Deeney JT, Matschinsky FM, Prentki M. A role for malonyl-CoA in glucose-stimulated insulin secretion from clonal pancreatic b-cells. J. Biol. Chem. 264(36), 21608-21612 (1989
22. Prentki M, Vischer S, Glennon MC, Regazzi R, Deeney JT, Corkey BE. Malonyl-CoA and long chain acyl-CoA esters as metabolic coupling factors in nutrient-induced insulin secretion. J. Biol. Chem. 267(9), 5802-5810 (1992
23. MacDonald MJ, Fahien LA, Brown LJ, Hasan NM, Buss JD, Kendrick MA. Perspective: emerging evidence for signaling roles of mitochondrial anaplerotic products in insulin secretion. Am. J. Physiol. Endocrinol. Metab. 288(1), E1-E15 (2005
24. Ronnebaum SM, Ilkayeva O, Burgess SC et al. A pyruvate cycling pathway involving cytosolic NADP-dependent isocitrate dehydrogenase regulates glucose-stimulated insulin secretion. J. Biol. Chem. 281(41), 30593-30602 (2006
25. Henquin JC, Nenquin M, Stiernet P, Ahren B. In vivo and in vitro glucose-induced biphasic insulin secretion in the mouse: pattern and role of cytoplasmic Ca2+ and amplification signals in b-cells. Diabetes 55(2), 441-451 (2006
26. MacDonald MJ, McKenzie DI, Walker TM, Kaysen JH. Lack of glyconeogenesis in pancreatic islets: expression of gluconeogenic enzyme genes in islets. Horm. Metab. Res. 24(4), 158-160 (1992
27. Sekine N, Cirulli V, Regazzi R et al. Low lactate dehydrogenase and high mitochondrial glycerol phosphate dehydrogenase in pancreatic b-cells. Potential role in nutrient sensing. J. Biol. Chem. 269(7), 4895-4902 (1994
28. MacDonald MJ. Feasibility of a mitochondrial pyruvate malate shuttle in pancreatic islets. Further implication of cytosolic NADPH in insulin secretion. J. Biol. Chem. 270(34), 20051-20058 (1995
29. Bavamian S, Klee P, Britan A et al. Islet-cell-to-cell communication as basis for normal insulin secretion. Diabetes Obes. Metab. 9(Suppl. 2), 118-132 (2007
30. De Leon DD, Stanley CA. Mechanisms of disease: advances in diagnosis and treatment of hyperinsulinism in neonates. Nat. Clin. Pract. Endocrinol. Metab. 3(1), 57-68 (2007
31. Stanley CA, Lieu YK, Hsu BY et al. Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene. N. Engl. J. Med. 338(19), 1352-1357 (1998
32. Glaser B, Kesavan P, Heyman M et al. Familial hyperinsulinism caused by an activating glucokinase mutation. N. Engl. J. Med. 338(4), 226-230 (1998
33. Clayton PT, Eaton S, Aynsley-Green A et al. Hyperinsulinism in short-chain L-3-hydroxyacyl-CoA dehydrogenase deficiency reveals the importance of b-oxidation in insulin secretion. J. Clin. Invest. 108(3), 457-465 (2001
34. Molven A, Matre GE, Duran M et al. Familial hyperinsulinemic hypoglycemia caused by a defect in the SCHAD enzyme of mitochondrial fatty acid oxidation. Diabetes 53(1), 221-227 (2004
35. Otonkoski T, Jiao H, Kaminen-Ahola N et al. Physical exercise-induced hypoglycemia caused by failed silencing of monocarboxylate transporter 1 in pancreatic b cells. Am. J. Hum. Genet. 81(3), 467-474 (2007
36. Otonkoski T, Kaminen N, Ustinov J et al. Physical exercise-induced hyperinsulinemic hypoglycemia is an autosomal-dominant trait characterized by abnormal pyruvate-induced insulin release. Diabetes 52(1), 199-204 (2003
37. Goossens A, Gepts W, Saudubray JM et al. Diffuse and focal nesidioblastosis. A clinicopathological study of 24 patients with persistent neonatal hyperinsulinemic hypoglycemia. Am. J. Surg. Pathol. 13(9), 766-775 (1989
38. Yakovac WC, Baker L, Hummeler K. B-cell nesidioblastosis in idiopathic hypoglycemia of infancy. J. Pediatr. 79(2), 226-231 (1971
39. Sempoux C, Guiot Y, Dubois D et al. Pancreatic B-cell proliferation in persistent hyperinsulinemic hypoglycemia of infancy: an immunohistochemical study of 18 cases. Mod. Pathol. 11(5), 444-449 (1998
40. Service FJ, Natt N, Thompson GB et al. Noninsulinoma pancreatogenous hypoglycemia: a novel syndrome of hyperinsulinemic hypoglycemia in adults independent of mutations in Kir6.2 and SUR1 genes. J. Clin. Endocrinol. Metab. 84(5), 1582-1589 (1999
41. Patti ME, McMahon G, Mun EC et al. Severe hypoglycaemia post-gastric bypass requiring partial pancreatectomy: evidence for inappropriate insulin secretion and pancreatic islet hyperplasia. Diabetologia 48(11), 2236-2240 (2005
42. Service GJ, Thompson GB, Service FJ, Andrews JC, Collazo-Clavell ML, Lloyd RV. Hyperinsulinemic hypoglycemia with nesidioblastosis after gastric-bypass surgery. N. Engl. J. Med. 353(3), 249-254 (2005
43. Meier JJ, Butler AE, Galasso R, Butler PC. Hyperinsulinemic hypoglycemia after gastric bypass surgery is not accompanied by islet hyperplasia or increased b-cell turnover. Diabetes Care 29(7), 1554-1559 (2006
44. Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC. b-cell deficit and increased b-cell apoptosis in humans with Type 2 diabetes. Diabetes 52(1), 102-110 (2003
45. Bonner-Weir S, Weir GC. New sources of pancreatic b-cells. Nat. Biotechnol. 23(7), 857-861 (2005
46. Meier JJ, Butler AE, Saisho Y et al. b-cell replication is the primary mechanism subserving the postnatal expansion of B-cell mass in humans. Diabetes 57(6), 1584-1594 (2008
47. Brelje TC, Scharp DW, Lacy PE et al. Effect of homologous placental lactogens, prolactins, and growth hormones on islet b-cell division and insulin secretion in rat, mouse, and human islets: implication for placental lactogen regulation of islet function during pregnancy. Endocrinology 132(2), 879-887 (1993
48. Van Assche FA, Aerts L, De Prins F. A morphological study of the endocrine pancreas in human pregnancy. Br. J. Obstet. Gynaecol. 85(11), 818-820 (1978
49. Ritzel RA, Butler AE, Rizza RA, Veldhuis JD, Butler PC. Relationship between b-cell mass and fasting blood glucose concentration in humans. Diabetes Care 29(3), 717-718 (2006
50. Georgia S, Bhushan A. b-cell replication is the primary mechanism for maintaining postnatal b cell mass. J. Clin. Invest. 114(7), 963-968 (2004
51. Dor Y, Brown J, Martinez OI, Melton DA. Adult pancreatic b-cells are formed by self-duplication rather than stem-cell differentiation. Nature 429(6987), 41-46 (2004
52. Alonso LC, Yokoe T, Zhang P et al. Glucose infusion in mice: a new model to induce b-cell replication. Diabetes 56(7), 1792 - 1801 (2007
53. Bonner-Weir S, Deery D, Leahy JL, Weir GC. Compensatory growth of pancreatic b-cells in adult rats after short-term glucose infusion. Diabetes 38(1), 49-53 (1989
54. Chick WL. b cell replication in rat pancreatic monolayer cultures. Effects of glucose, tolbutamide, glucocorticoid, growth hormone and glucagon 1. Diabetes 22(9), 687-693 (1973
55. Ueki K, Okada T, Hu J et al. Total insulin and IGF-I resistance in pancreatic b cells causes overt diabetes. Nat. Genet. 38(5), 583-588 (2006
56. Perfetti R, Zhou J, Doyle ME, Egan JM. Glucagon-like peptide-1 induces cell proliferation and pancreatic-duodenum homeobox-1 expression and increases endocrine cell mass in the pancreas of old, glucose-intolerant rats. Endocrinology 141(12), 4600-4605 (2000
57. Withers DJ, Gutierrez JS, Towery H et al. Disruption of IRS-2 causes Type 2 diabetes in mice. Nature 391(6670), 900-904 (1998
58. Kushner JA, Ye J, Schubert M et al. Pdx1 restores b-cell function in Irs2 knockout mice. J. Clin. Invest. 109(9), 1193-1201 (2002
59. Terauchi Y, Takamoto I, Kubota N et al. Glucokinase and IRS-2 are required for compensatory b-cell hyperplasia in response to high-fat diet-induced insulin resistance. J. Clin. Invest. 117(1), 246-257 (2007
60. Jhala US, Canettieri G, Screaton RA et al. cAMP promotes pancreatic b-cell survival via CREB-mediated induction of IRS2. Genes Dev. 17(13), 1575-1580 (2003
61. Lingohr MK, Briaud I, Dickson LM et al. Specific regulation of IRS-2 expression by glucose in rat primary pancreatic islet b-cells. J. Biol. Chem. 281(23), 15884-15892 (2006
62. Screaton RA, Conkright MD, Katoh Y et al. The CREB coactivator TORC2 functions as a calcium- and cAMP-sensitive coincidence detector. Cell 119(1), 61-74 (2004
63. Tuttle RL, Gill NS, Pugh W et al. Regulation of pancreatic b-cell growth and survival by the serine/threonine protein kinase Akt1/PKBa. Nat. Med. 7(10), 1133-1137 (2001
64. Bernal-Mizrachi E, Wen W, Stahlhut S, Welling CM, Permutt MA. Islet b cell expression of constitutively active Akt1/ PKB a induces striking hypertrophy, hyperplasia, and hyperinsulinemia. J. Clin. Invest. 108(11), 1631-1638 (2001
65. Kitamura T, Nakae J, Kitamura Y et al. The forkhead transcription factor Foxo1 links insulin signaling to Pdx1 regulation of pancreatic b cell growth. J. Clin. Invest. 110(12), 1839-1847 (2002
66. Uchida T, Nakamura T, Hashimoto N et al. Deletion of Cdkn1b ameliorates hyperglycemia by maintaining compensatory hyperinsulinemia in diabetic mice. Nat. Med. 11(2), 175-182 (2005
67. Tanabe K, Liu Z, Patel S et al. Genetic deficiency of glycogen synthase kinase-3b corrects diabetes in mouse models of insulin resistance. PLoS Biol. 6(2), e37 (2008
68. Pende M, Kozma SC, Jaquet M et al. Hypoinsulinaemia, glucose intolerance and diminished b-cell size in S6K1- deficient mice. Nature 408(6815), 994-997 (2000
69. Alliouachene S, Tuttle RL, Boumard S et al. Constitutively active Akt1 expression in mouse pancreas requires S6 kinase 1 for insulinoma formation. J. Clin. Invest. 118(11), 3629-3638 (2008
70. Johnson JD, Bernal-Mizrachi E, Alejandro EU et al. Insulin protects islets from apoptosis via Pdx1 and specific changes in the human islet proteome. Proc. Natl Acad. Sci. USA 103(51), 19575-19580 (2006
71. Elghazi L, Rachdi L, Weiss AJ, Cras-Meneur C, Bernal-Mizrachi E. Regulation of b-cell mass and function by the Akt/protein kinase B signalling pathway. Diabetes Obes. Metab. 9(Suppl. 2), 147-157 (2007
72. Steiner DF, Oyer PE. The biosynthesis of insulin and a probable precursor of insulin by a human islet cell adenoma. Proc. Natl Acad. Sci. USA 57(2), 473-480 (1967
73. Rhodes CJ. Diabetes mellitus In: A Fundamental and Clinical Text. LeRoith D, Taylor SI, Olefsky JM,(Eds). Lippincott Williams & Wilkins, PA, USA 27-50 (2004
74. Orci L, Ravazzola M, Storch MJ, Anderson RG, Vassalli JD, Perrelet A. Proteolytic maturation of insulin is a post-Golgi event which occurs in acidifying clathrin-coated secretory vesicles. Cell 49(6), 865-868 (1987
75. Davidson HW, Rhodes CJ, Hutton JC. Intraorganellar calcium and pH control proinsulin cleavage in the pancreatic b cell via two distinct site-specific endopeptidases. Nature 333(6168), 93-96 (1988
76. Smeekens SP, Montag AG, Thomas G et al. Proinsulin processing by the subtilisin-related proprotein convertases furin, PC2, and PC3. Proc. Natl Acad. Sci. USA 89(18), 8822-8826 (1992
77. Davidson HW, Hutton JC. The insulin-secretory-granule carboxypeptidase H. Purification and demonstration of involvement in proinsulin processing. Biochem. J. 245(2), 575-582 (1987
78. Roth J, Gorden P, Pastan I. "Big insulin": a new component of plasma insulin detected by immunoassay. Proc. Natl Acad. Sci. USA 61(1), 138-145 (1968
79. Lazarus NR, Tanese T, Gutman R, Recant L. Synthesis and release of proinsulin and insulin by human insulinoma tissue. J. Clin. Endocrinol. Metab. 30(3), 273-281 (1970
80. Gorden P, Sherman B, Roth J. Proinsulin-like component of circulating insulin in the basal state and in patients and hamsters with islet cell tumors. J. Clin. Invest. 50(10), 2113-2122 (1971
81. Gutman RA, Lazarus NR, Penhos JC, Fajans S, Recant L. Circulating proinsulin-like material in patients with functioning insulinomas. N. Engl. J. Med. 284(18), 1003-1008 (1971
82. Sherman BM, Pek S, Fajans SS, Floyd JC Jr, Conn JW. Plasma proinsulin in patients with functioning pancreatic islet cell tumors. J. Clin. Endocrinol. Metab. 35(2), 271-280 (1972
83. Gorden P, Skarulis MC, Roach P et al. Plasma proinsulin-like component in insulinoma: a 25-year experience. J. Clin. Endocrinol. Metab. 80(10), 2884-2887 (1995
84. Halban PA, Irminger JC. Sorting and processing of secretory proteins. Biochem. J. 299(Pt 1), 1-18 (1994
85. Irminger JC, Vollenweider FM, Neerman- Arbez M, Halban PA. Human proinsulin conversion in the regulated and the constitutive pathways of transfected AtT20 cells. J. Biol. Chem. 269(3), 1756-1762 (1994
86. Nagamatsu S, Steiner DF. Altered glucose regulation of insulin biosynthesis in insulinoma cells: mouse b TC3 cells secrete insulin-related peptides predominantly via a constitutive pathway. Endocrinology 130(2), 748-754 (1992
87. Kao PC, Taylor RL, Service FJ. Proinsulin by immunochemiluminometric assay for the diagnosis of insulinoma. J. Clin. Endocrinol. Metab. 78(5), 1048-1051 (1994
88. Service FJ, McMahon MM, O'Brien PC, Ballard DJ. Functioning insulinoma - incidence, recurrence, and long-term survival of patients: a 60-year study. Mayo Clin. Proc. 66(7), 711-719 (1991
89. Marx S, Spiegel AM, Skarulis MC, Doppman JL, Collins FS, Liotta LA. Multiple endocrine neoplasia type 1: clinical and genetic topics. Ann. Intern. Med. 129(6), 484-494 (1998
90. Anlauf M, Bauersfeld J, Raffel A et al. Insulinomatosis: a multicentric insulinoma disease that frequently causes early recurrent hyperinsulinemic hypoglycemia. Am. J. Surg. Pathol. 33(3) (2009
91. Anlauf M, Schlenger R, Perren A et al. Microadenomatosis of the endocrine pancreas in patients with and without the multiple endocrine neoplasia type 1 syndrome. Am. J. Surg. Pathol. 30(5), 560-574 (2006
92. Guettier JM, Kam A, Chang R et al. Localization of insulinomas to regions of the pancreas by intraarterial calcium stimulation: the NIH experience. J. Clin. Endocrinol. Metab. 94(4), 1074-1080 (2009
93. Hirshberg B, Livi A, Bartlett DL et al. Forty-eight-hour fast: the diagnostic test for insulinoma. J. Clin. Endocrinol. Metab. 85(9), 3222-3226 (2000
94. Hirshberg B, Cochran C, Skarulis MC et al. Malignant insulinoma: spectrum of unusual clinical features. Cancer 104(2), 264-272 (2005
95. Guettier JM, Gorden P. Hypoglycemia. Endocrinol. Metab. Clin. North Am. 35(4), 753ix-757ix (2006
96. Marx SJ, Simonds WF. Hereditary hormone excess: genes, molecular pathways, and syndromes. Endocr. Rev. 26(5), 615-661 (2005
97. Perren A, Roth J, Muletta-Feurer S et al. Clonal analysis of sporadic pancreatic endocrine tumours. J. Pathol. 186(4), 363-371 (1998
98. Barghorn A, Komminoth P, Bachmann D et al. Deletion at 3p25.3-p23 is frequently encountered in endocrine pancreatic tumours and is associated with metastatic progression. J. Pathol. 194(4), 451-458 (2001
99. Barghorn A, Speel EJ, Farspour B et al. Putative tumor suppressor loci at 6q22 and 6q23-q24 are involved in the malignant progression of sporadic endocrine pancreatic tumors. Am. J. Pathol. 158(6), 1903-1911 (2001
100. Speel EJ, Richter J, Moch H et al. Genetic differences in endocrine pancreatic tumor subtypes detected by comparative genomic hybridization. Am. J. Pathol. 155(6), 1787-1794 (1999
101. Zhao J, Moch H, Scheidweiler AF et al. Genomic imbalances in the progression of endocrine pancreatic tumors. Genes Chromosomes Cancer 32(4), 364-372 (2001
102. Jonkers YM, Claessen SM, Perren A et al. Chromosomal instability predicts metastatic disease in patients with insulinomas. Endocr. Relat. Cancer 12(2), 435-447 (2005
103. Zhuang Z, Vortmeyer AO, Pack S et al. Somatic mutations of the MEN1 tumor suppressor gene in sporadic gastrinomas and insulinomas. Cancer Res. 57(21), 4682-4686 (1997
104. Arnold CN, Sosnowski A, Schmitt-Graff A, Arnold R, Blum HE. Analysis of molecular pathways in sporadic neuroendocrine tumors of the gastro-entero- pancreatic system. Int. J. Cancer 120(10), 2157-2164 (2007
105. Pelengaris S, Khan M, Evan GI. Suppression of Myc-induced apoptosis in b cells exposes multiple oncogenic properties of Myc and triggers carcinogenic progression. Cell 109(3), 321-334 (2002
106. Creutzfeldt W, Creutzfeldt C, Frerichs H, Track NS, Arnold R. Histochemistry, ultrastructure and hormone content of human insulinomas. Horm. Metab. Res. (Suppl. 6), 7-18 (1976
107. Minn AH, Kayton M, Lorang D et al. Insulinomas and expression of an insulin splice varient. Lancet 363(9406), 363-373 (2004
108. Placzkowski KA, Vella A, Thompson GB et al. Secular trends in the presentation and management of functioning insulinoma at the Mayo Clinic, 1987-2007. J. Clin. Endocrinol. Metab. 94(4), 1069-1073 (2009
109. Brown CK, Bartlett DL, Doppman JL et al. Intraarterial calcium stimulation and intraoperative ultrasonography in the localization and resection of insulinomas. Surgery 122(6), 1189-1193 (1997
110. Pitre J, Soubrane O, Palazzo L, Chapuis Y. Endoscopic ultrasonography for the preoperative localization of insulinomas. Pancreas 13(1), 55-60 (1996
111. Schumacher B, Lubke HJ, Frieling T, Strohmeyer G, Starke AA. Prospective study on the detection of insulinomas by endoscopic ultrasonography. Endoscopy 28(3), 273-276 (1996
112. Ardengh JC, Rosenbaum P, Ganc AT et al. Role of EUS in the preoperative localization of insulinomas compared with spiral CT. Gastrointest. Endosc. 51(5), 552-555 (2000
113. Nesje LB, Varhaug JE, Husebye ES, Odegaard S. Endoscopic ultrasonography for preoperative diagnosis and localization of insulinomas. Scand. J. Gastroenterol. 37(6), 732-737 (2002
114. Zimmer T, Stolzel U, Bader M et al. Endoscopic ultrasonography and somatostatin receptor scintigraphy in the preoperative localisation of insulinomas and gastrinomas. Gut 39(4), 562-568 (1996
115. Krenning EP, Kwekkeboom DJ, Oei HY et al. Somatostatin-receptor scintigraphy in gastroenteropancreatic tumors. An overview of European results. Ann. NY Acad. Sci. 733, 416-424 (1994
116. van Eyck CH, Bruining HA, Reubi JC et al. Use of isotope-labeled somatostatin analogs for visualization of islet cell tumors. World J. Surg. 17(4), 444-447 (1993
117. Oberg K, Astrup L, Eriksson B et al. Guidelines for the management of gastroenteropancreatic neuroendocrine tumours (including bronchopulmonary and thymic neoplasms). Part I - general overview. Acta Oncol. 43(7), 617-625 (2004
118. Oberg K. Somatostatin analog octreotide LAR in gastro-entero-pancreatic tumors. Expert Rev. Anticancer. Ther. 9(5), 557-566 (2009
119. Kauhanen S, Seppanen M, Minn H et al. Fluorine-18-l- dihydroxyphenylalanine (18F-DOPA) positron emission tomography as a tool to localize an insulinoma or b-cell hyperplasia in adult patients. J. Clin. Endocrinol. Metab. 92(4), 1237-1244 (2007
120. Wild D, Macke H, Christ E, Gloor B, Reubi JC. Glucagon-like peptide 1-receptor scans to localize occult insulinomas. N. Engl. J. Med. 359(7), 766-768 (2008)