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Insulinoma cell CaSR influences insulin secretion in a case with concurrent familial hypocalciuric hypercalcemia and malignant metastatic insulinoma.

Y Ono, Internal Medicine, Fujita Health University School of Medicine, Toyoake, Japan
N Oda, Internal Medicine, Fujita Health University School of Medicine, Toyoake-City, 470-1192, Japan
S Ishihara, Department of Surgery, Fujita Health University School of Medicine, toyoake, Japan
A Shimomura, Department of Anatomy, Fujita Health University School of Medicine, Toyoake, Japan
N Hayakawa, Internal Medicine, Fujita Health University School of Medicine, Toyoake, Japan
A Suzuki, Internal Medicine, Fujita Health University School of Medicine, Toyoake, Japan
A Horiguchi, Department of Surgery, Fujita Health University School of Medicine, toyoake, Japan
T Senda, Department of Anatomy, Fujita Health University School of Medicine, Toyoake, Japan
S Miyakawa, Department of Surgery, Fujita Health University School of Medicine, toyoake, Japan
M Itoh, Internal Medicine, Fujita Health University School of Medicine, Toyoake, Japan

Correspondence: Naohisa Oda, Email: naohisa{at}fujita-hu.ac.jp

Abstract

Context and 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.

Design and Patient

The patient with FHH also suffered from insulinoma. We reasoned that insulin secretion for ASVS is dependent on the calcium sensing receptor (CaSR). AVSV 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 MEN1 gene. In addition, expression of both CaSR mRNA and CaSR protein was confirmed in the insulinoma samples.

Conclusion

These results suggest that the CaSR gene is involved in ASVS-induced insulin secretion.