title: Insulinoma cell calcium-sensing receptor influences insulin secretion in a case with concurrent familial hypocalciuric hypercalcemia and malignant metastatic insulinoma.
abstract: 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.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan.
authors.forename: Yasunaga
authors.initials: Y
authors.lastname: Ono
authors.forename: Naohisa
authors.initials: N
authors.lastname: Oda
authors.forename: Shin
authors.initials: S
authors.lastname: Ishihara
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shimomura
authors.forename: Nobuki
authors.initials: N
authors.lastname: Hayakawa
authors.forename: Atsushi
authors.initials: A
authors.lastname: Suzuki
authors.forename: Akihiko
authors.initials: A
authors.lastname: Horiguchi
authors.forename: Takao
authors.initials: T
authors.lastname: Senda
authors.forename: Shuichi
authors.initials: S
authors.lastname: Miyakawa
authors.forename: Mitsuyasu
authors.initials: M
authors.lastname: Itoh
mesh_terms: 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
chemical_list: D007328:Insulin; D044169:Receptors, Calcium-Sensing