click to enlarge

Regulation of energy balance is fundamental to homeostasis, and probably has sex-specific attributes. LEAP2 is a liver-derived ghrelin receptor (GHSR1a) antagonist that counteracts ghrelin’s effects on appetite, but its influence on pancreatic islet hormone release is less understood.

Hewawasam et al. examined how acyl-ghrelin (AG) and LEAP2 regulate hormone secretion using isolated pancreatic islets from male and female mice. Using radioimmunoassay and quantitative PCR, they found that LEAP2 enhanced insulin secretion in males but not in females. Neither AG nor LEAP2 significantly affected glucagon release. Analysis showed no sex-based differences in Ghsr1a, Ghrelin, Leap2, Mrap2, Mboat4 or Sstr3 mRNA expression. However, MK4256, a somatostatin receptor antagonist, enhanced glucose-stimulated insulin secretion in males. In male islets without 17β-oestradiol (E2), AG reduced insulin secretion, an effect partially reversed by LEAP2. E2 pre-treatment abolished these responses. LEAP2 also suppressed AG-stimulated somatostatin release in untreated, but not in E2-treated, islets.

This study reveals that LEAP2 and AG modulate insulin and somatostatin release in a sex-dependent manner, with E2 influencing male responses. This suggests that somatostatin release modulation is critical to the role of GHSR1a in islet function and glucose regulation.

Read the full article in Journal of Endocrinology 263 e240135 https://doi.org/10.1530/JOE-24-0135