Elevated blood levels of liver-expressed antimicrobial peptide 2 in patients with insulinoma and its expression in insulinomas.

OBJECTIVE: Most patients with insulinoma are overweight or obese. Ghrelin levels in insulinoma have been linked to both obesity and hyperinsulinemia. Liver-expressed antimicrobial peptide 2 (LEAP2), a novel hormone and endogenous antagonist of the ghrelin receptor, is associated with obesity; however, its relationship with obesity and hyperinsulinemia in insulinoma, and its expression within tumor tissue, remains unknown. METHODS: Serum LEAP2, insulin, and ghrelin levels were measured by ELISA in patients with insulinoma and in age-, sex-, and BMI-matched controls. LEAP2 expression was examined in insulinoma tissue and paired adjacent pancreatic specimens by immunohistochemical staining. RESULTS: Serum LEAP2 levels were significantly higher in patients with insulinoma than in controls (P = 0.028) and positively correlated with serum insulin levels (r = 0.408, P < 0.001) while negatively correlated with ghrelin levels (r = -0.551, P < 0.01). In controls, serum LEAP2 levels were significantly associated with BMI (P = 0.047), whereas in patients, the correlation did not reach statistical significance (P = 0.067). Immunostaining showed that LEAP2 peptide was expressed in insulinoma tissue. CONCLUSION: Serum LEAP2 levels are elevated in insulinoma and correlate with hyperinsulinemia and BMI. LEAP2 is expressed in insulinoma tissue, suggesting a potential role in the metabolic profile of these patients.