Insulin Secretion and Insulin-producing Tumors

Overview

Journal Expert Rev Endocrinol Metab

Specialty Endocrinology

Date 2010 Apr 20

PMID 20401170

Citations 13

Authors

Jean-Marc Guettier

Phillip Gorden

Affiliations

Soon will be listed here.

Abstract

Insulinomas are rare neuroendocrine tumors of pancreatic islet cells that retain the ability to produce and secrete insulin. In contrast to normally differentiated β-cells, insulinoma cells continue to secrete insulin and proinsulin at low blood glucose. This deregulated insulin secretion manifests clinically as fasting hypoglycemia. The molecular pathways that characterize normal insulin secretion and β-cell growth are reviewed and contrasted to the biology of insulinomas. The second half of this review summarizes the clinical approach to the disorder. The diagnosis of insulinoma is established by demonstrating inappropriately high insulin levels with coincident hypoglycemia at the time of a supervised fast. Localization of insulinomas is challenging owing to their small size but should be attempted to maximize the chance for successful surgical resection and avoid risks associated with reoperation. In the majority of cases, successful surgical resection leads to lifelong cure.

Citing Articles

Diagnosis and management of benign secreting pancreatic insulinoma: What's new? 4 case report.

Bahou K, Achour Y, Ilahiane M, Sekkat H, Bakali Y, Mhamdi Alaoui M Rare Tumors. 2025; 17():20363613241313409.

PMID: 39790868 PMC: 11713962. DOI: 10.1177/20363613241313409.

Genotype-histotype-phenotype correlations in hyperinsulinemic hypoglycemia.

Larsen A, Brusgaard K, Christesen H, Detlefsen S Histol Histopathol. 2024; 39(7):817-844.

PMID: 38305063 DOI: 10.14670/HH-18-709.

Identifying target ion channel-related genes to construct a diagnosis model for insulinoma.

Mo S, Wang Y, Wu W, Zhao H, Jiang H, Qin S Front Genet. 2023; 14:1181307.

PMID: 37772258 PMC: 10523017. DOI: 10.3389/fgene.2023.1181307.

Characterization of the Secretome, Transcriptome, and Proteome of Human β Cell Line EndoC-βH1.

Ryaboshapkina M, Saitoski K, Hamza G, Jarnuczak A, Pechberty S, Berthault C Mol Cell Proteomics. 2022; 21(5):100229.

PMID: 35378291 PMC: 9062487. DOI: 10.1016/j.mcpro.2022.100229.

Microtubules and Gαo-signaling modulate the preferential secretion of young insulin secretory granules in islet β cells via independent pathways.

Hu R, Zhu X, Yuan M, Ho K, Kaverina I, Gu G PLoS One. 2021; 16(7):e0241939.

PMID: 34292976 PMC: 8297875. DOI: 10.1371/journal.pone.0241939.

References

Pelengaris S, Khan M, Evan G . Suppression of Myc-induced apoptosis in beta cells exposes multiple oncogenic properties of Myc and triggers carcinogenic progression. Cell. 2002; 109(3):321-34. DOI: 10.1016/s0092-8674(02)00738-9. View

MacDonald M, McKenzie D, Walker T, Kaysen J . Lack of glyconeogenesis in pancreatic islets: expression of gluconeogenic enzyme genes in islets. Horm Metab Res. 1992; 24(4):158-60. DOI: 10.1055/s-2007-1003284. View

Barghorn A, Komminoth P, Bachmann D, Rutimann K, Saremaslani P, Perren A . Deletion at 3p25.3-p23 is frequently encountered in endocrine pancreatic tumours and is associated with metastatic progression. J Pathol. 2001; 194(4):451-8. DOI: 10.1002/path.886. View

Alliouachene S, Tuttle R, Boumard S, Lapointe T, Berissi S, Germain S . Constitutively active Akt1 expression in mouse pancreas requires S6 kinase 1 for insulinoma formation. J Clin Invest. 2008; 118(11):3629-38. PMC: 2564609. DOI: 10.1172/JCI35237. View

Smeekens S, Montag A, Thomas G, Albiges-Rizo C, Carroll R, Benig M . Proinsulin processing by the subtilisin-related proprotein convertases furin, PC2, and PC3. Proc Natl Acad Sci U S A. 1992; 89(18):8822-6. PMC: 50013. DOI: 10.1073/pnas.89.18.8822. View

Oberg K . Somatostatin analog octreotide LAR in gastro-entero-pancreatic tumors. Expert Rev Anticancer Ther. 2009; 9(5):557-66. DOI: 10.1586/era.09.26. View

Kao P, Taylor R, Service F . Proinsulin by immunochemiluminometric assay for the diagnosis of insulinoma. J Clin Endocrinol Metab. 1994; 78(5):1048-51. DOI: 10.1210/jcem.78.5.8175958. View

Bonner-Weir S, Deery D, Leahy J, Weir G . Compensatory growth of pancreatic beta-cells in adult rats after short-term glucose infusion. Diabetes. 1989; 38(1):49-53. DOI: 10.2337/diab.38.1.49. View

Chick W . Beta cell replication in rat pancreatic monolayer cultures. Effects of glucose, tolbutamide, glucocorticoid, growth hormone and glucagon. Diabetes. 1973; 22(9):687-93. DOI: 10.2337/diab.22.9.687. View

10.

Stanley C, Lieu Y, Hsu B, Burlina A, Greenberg C, Hopwood N . Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene. N Engl J Med. 1998; 338(19):1352-7. DOI: 10.1056/NEJM199805073381904. View

11.

Eto K, Suga S, Wakui M, Tsubamoto Y, Terauchi Y, Taka J . 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. 1999; 274(36):25386-92. DOI: 10.1074/jbc.274.36.25386. View

12.

Bonner-Weir S, Weir G . New sources of pancreatic beta-cells. Nat Biotechnol. 2005; 23(7):857-61. DOI: 10.1038/nbt1115. View

13.

Van Assche F, Aerts L, De Prins F . A morphological study of the endocrine pancreas in human pregnancy. Br J Obstet Gynaecol. 1978; 85(11):818-20. DOI: 10.1111/j.1471-0528.1978.tb15835.x. View

14.

De Leon D, Stanley C . Mechanisms of Disease: advances in diagnosis and treatment of hyperinsulinism in neonates. Nat Clin Pract Endocrinol Metab. 2006; 3(1):57-68. DOI: 10.1038/ncpendmet0368. View

15.

Uchida T, Nakamura T, Hashimoto N, Matsuda T, Kotani K, Sakaue H . Deletion of Cdkn1b ameliorates hyperglycemia by maintaining compensatory hyperinsulinemia in diabetic mice. Nat Med. 2005; 11(2):175-82. DOI: 10.1038/nm1187. View

16.

Gerich J, Charles M, GRODSKY G . Characterization of the effects of arginine and glucose on glucagon and insulin release from the perfused rat pancreas. J Clin Invest. 1974; 54(4):833-41. PMC: 301623. DOI: 10.1172/JCI107823. View

17.

PITRE J, Soubrane O, Palazzo L, Chapuis Y . Endoscopic ultrasonography for the preoperative localization of insulinomas. Pancreas. 1996; 13(1):55-60. DOI: 10.1097/00006676-199607000-00007. View

18.

Tanabe K, Liu Z, Patel S, Doble B, Li L, Cras-Meneur C . Genetic deficiency of glycogen synthase kinase-3beta corrects diabetes in mouse models of insulin resistance. PLoS Biol. 2008; 6(2):e37. PMC: 2245985. DOI: 10.1371/journal.pbio.0060037. View

19.

Screaton R, Conkright M, Katoh Y, Best J, Canettieri G, Jeffries S . The CREB coactivator TORC2 functions as a calcium- and cAMP-sensitive coincidence detector. Cell. 2004; 119(1):61-74. DOI: 10.1016/j.cell.2004.09.015. View

20.

Thorens B, Sarkar H, Kaback H, Lodish H . Cloning and functional expression in bacteria of a novel glucose transporter present in liver, intestine, kidney, and beta-pancreatic islet cells. Cell. 1988; 55(2):281-90. DOI: 10.1016/0092-8674(88)90051-7. View