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

**Authors:** Jia-Lei Zhang, An-Li Tong, Yun-Lu Feng, Da-Chun Zhao, Ling Zhong, Yin-Jie Gao, Yu-Li Song, Tai-Ping Zhang, Ming Li, Yuan-Jia Chen

PMC · DOI: 10.3389/fendo.2025.1685806 · Frontiers in Endocrinology · 2025-12-19

## TL;DR

This study finds elevated levels of LEAP2 in insulinoma patients, linking it to hyperinsulinemia and suggesting a role in the disease's metabolic profile.

## Contribution

The study is the first to show elevated LEAP2 in insulinoma patients and its expression in tumor tissue.

## Key findings

- Serum LEAP2 levels are significantly higher in insulinoma patients compared to controls.
- LEAP2 positively correlates with insulin levels and negatively with ghrelin in insulinoma patients.
- LEAP2 is expressed in insulinoma tissue, indicating a potential metabolic role.

## Abstract

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.

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.

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.

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.

## Linked entities

- **Proteins:** LEAP2 (liver enriched antimicrobial peptide 2), GHRL (ghrelin and obestatin prepropeptide)
- **Diseases:** insulinoma (MONDO:0024677), obesity (MONDO:0011122)

## Full-text entities

- **Genes:** LEAP2 (liver enriched antimicrobial peptide 2) [NCBI Gene 116842] {aka LEAP-2}, GHSR (growth hormone secretagogue receptor) [NCBI Gene 2693] {aka GHDP, GHS-R1a, GHSR-1a}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}
- **Diseases:** obese (MESH:D009765), tumor (MESH:D009369), overweight (MESH:D050177), insulinoma (MESH:D007340), hyperinsulinemia (MESH:D006946)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12757234/full.md

## References

48 references — full list in the complete paper: https://tomesphere.com/paper/PMC12757234/full.md

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Source: https://tomesphere.com/paper/PMC12757234