Insulinoma cell calcium-sensing receptor influences insulin secretion in a case with concurrent familial hypocalciuric hypercalcemia and malignant metastatic insulinoma.
OBJECTIVE
Arterial stimulation and venous sampling (ASVS) is an important technique for localizing insulinoma. The principle behind ASVS is that insulin secretion is promoted from insulinoma cells by the injection of calcium into the insulinoma-feeding artery. However, the mechanism for ASVS-induced insulin secretion remains unclear. Both insulinoma and familial hypocalciuric hypercalcemia (FHH) are rare diseases. This study reports on a case in which both of these diseases occur concurrently.


METHODS
The patient with FHH also suffered from insulinoma. We reasoned that insulin secretion for ASVS is dependent on the calcium-sensing receptor (CaSR). ASVS was performed on this patient. The expression of the CaSR protein and corresponding mRNA were confirmed.


RESULTS
No significant changes in the plasma levels of insulin and C-peptide were observed during ASVS. The patient was clinically diagnosed as having FHH. We confirmed that a mutation in the CaSR gene was present in the genomic DNA of this patient and that there were no mutations in the multiple endocrine neoplasia type 1 gene. In addition, expression of both CaSR mRNA and CaSR protein was confirmed in the insulinoma samples.


CONCLUSIONS
These results suggest that the CaSR gene is involved in ASVS-induced insulin secretion.
Ono
Yasunaga
Y
Division of Endocrinology and Metabolism, Department of Internal Medicine, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan.
Oda
Naohisa
N
Ishihara
Shin
S
Shimomura
Atsushi
A
Hayakawa
Nobuki
N
Suzuki
Atsushi
A
Horiguchi
Akihiko
A
Senda
Takao
T
Miyakawa
Shuichi
S
Itoh
Mitsuyasu
M
D015153:Blotting, Western; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism; D007340:Insulinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D010179:Pancreas / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D011877:Radionuclide Imaging; D044169:Receptors, Calcium-Sensing / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014057:Tomography, X-Ray Computed
D007328:Insulin; D044169:Receptors, Calcium-Sensing