Peak stimulated insulin secretion is associated with specific changes in gene expression profiles in sporadic insulinomas

Mark L. Kayton, Nick G. Costouros, Dominique Lorang, H. Richard Alexander, Stephen M. Hewitt, Craig Cochran, Anath Shalev, David Harlan, Monica C. Skarulis, Philip Gorden, Steven K. Libutti, Sareh Parangi, Masayuki Imamura, Richard A. Hodin, Martha A. Zeiger

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background. The molecular pathways that are responsible for pathologic insulin secretion by insulinomas have not been characterized. We studied gene expression profiles from insulinomas and determined associations between these changes and preoperative peak serum insulin levels. Methods. Ten patients with insulinomas underwent calcium-stimulated arteriography and surgical resection. Tumor RNA was isolated; corresponding complementary DNA was hybridized to 10K human complementary DNA arrays. Pooled human islet cell complementary DNA served as the control. Cluster analysis of gene expression and analysis of expression ratios was performed. Results. Nineteen genes were up-regulated at least 3-fold in insulinomas compared with controls, which included the genes for islet amyloid polypeptide and proprotein convertase type 2. Cluster analysis revealed 2 groups of patients with insulinoma and with distinct patterns of gene expression. Mean peak serum insulin values between groups were 196 and 1100 (U/mL (P < .05), which demonstrates a significant difference in insulin response to calcium stimulation between these 2 groups. Conclusion. We show that genes that are relevant to the pathogenesis of hyperinsulinemia are expressed preferentially in insulinomas. In addition, patients with a distinct and common pattern of gene expression had significantly higher stimulated insulin secretion levels. The study of these genes may help to identify the biochemical pathways that are responsible for pathologic insulin secretion.

Original languageEnglish (US)
Pages (from-to)982-988
Number of pages7
JournalSurgery
Volume134
Issue number6
DOIs
StatePublished - Dec 2003
Externally publishedYes

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Insulinoma
Transcriptome
Insulin
Complementary DNA
Gene Expression
Genes
Cluster Analysis
Proprotein Convertase 2
Islet Amyloid Polypeptide
Calcium
Hyperinsulinism
Oligonucleotide Array Sequence Analysis
Serum
Islets of Langerhans
Angiography
RNA
Neoplasms

ASJC Scopus subject areas

  • Surgery

Cite this

Kayton, M. L., Costouros, N. G., Lorang, D., Alexander, H. R., Hewitt, S. M., Cochran, C., ... Zeiger, M. A. (2003). Peak stimulated insulin secretion is associated with specific changes in gene expression profiles in sporadic insulinomas. Surgery, 134(6), 982-988. https://doi.org/10.1016/j.surg.2003.07.011

Peak stimulated insulin secretion is associated with specific changes in gene expression profiles in sporadic insulinomas. / Kayton, Mark L.; Costouros, Nick G.; Lorang, Dominique; Alexander, H. Richard; Hewitt, Stephen M.; Cochran, Craig; Shalev, Anath; Harlan, David; Skarulis, Monica C.; Gorden, Philip; Libutti, Steven K.; Parangi, Sareh; Imamura, Masayuki; Hodin, Richard A.; Zeiger, Martha A.

In: Surgery, Vol. 134, No. 6, 12.2003, p. 982-988.

Research output: Contribution to journalArticle

Kayton, ML, Costouros, NG, Lorang, D, Alexander, HR, Hewitt, SM, Cochran, C, Shalev, A, Harlan, D, Skarulis, MC, Gorden, P, Libutti, SK, Parangi, S, Imamura, M, Hodin, RA & Zeiger, MA 2003, 'Peak stimulated insulin secretion is associated with specific changes in gene expression profiles in sporadic insulinomas', Surgery, vol. 134, no. 6, pp. 982-988. https://doi.org/10.1016/j.surg.2003.07.011
Kayton, Mark L. ; Costouros, Nick G. ; Lorang, Dominique ; Alexander, H. Richard ; Hewitt, Stephen M. ; Cochran, Craig ; Shalev, Anath ; Harlan, David ; Skarulis, Monica C. ; Gorden, Philip ; Libutti, Steven K. ; Parangi, Sareh ; Imamura, Masayuki ; Hodin, Richard A. ; Zeiger, Martha A. / Peak stimulated insulin secretion is associated with specific changes in gene expression profiles in sporadic insulinomas. In: Surgery. 2003 ; Vol. 134, No. 6. pp. 982-988.
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