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


CONCLUSIONS
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.
Kayton
Mark L
ML
Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 10, 10 Center Drive, Bethesda, MD 20892, USA.
Costouros
Nick G
NG
Lorang
Dominique
D
Alexander
H Richard
HR
Hewitt
Stephen M
SM
Cochran
Craig
C
Shalev
Anath
A
Harlan
David
D
Skarulis
Monica C
MC
Gorden
Philip
P
Libutti
Steven K
SK
D000328:Adult; D000368:Aged; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D006801:Humans; D007328:Insulin / Q000096:biosynthesis* / Q000235:genetics*; D007340:Insulinoma / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010180:Pancreatectomy / Q000379:methods; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D012334:RNA, Neoplasm / Q000032:analysis; D015854:Up-Regulation / Q000235:genetics
D007328:Insulin; D012334:RNA, Neoplasm