LEAP2 Regulates Insulin Secretion from INS-1E Beta Cells and Rat Pancreatic Islets: An In Vitro Study

LEAP2 is an endogenous antagonist and inverse agonist of GHSR-1a, the receptor for acyl-ghrelin. Although LEAP2 is increasingly recognized as a regulator of appetite and glucose homeostasis, its direct effects on pancreatic endocrine cells remain incompletely understood. The present in vitro study evaluated whether LEAP2 modulates insulin secretion and the expression of insulin-related genes in INS-1E beta cells and isolated rat pancreatic islets. LEAP2 treatment altered selected components of the insulin-related expression profile in a model- and time-dependent manner. In INS-1E cells, LEAP2 increased insulin protein expression after 6 h and IRSII protein expression after 24 h, whereas effects on mRNA expression were variable. In isolated rat islets, LEAP2 increased INS2 mRNA expression and decreased GHSR-1a and preproghrelin mRNA expression under the tested conditions. Acute exposure to 100 nM LEAP2 increased basal insulin release from both INS-1E cells and isolated islets. Immunofluorescence and Western blot analyses detected LEAP2- and GHSR-1a-related immunoreactivity in pancreatic models. LEAP2 did not adversely affect INS-1E cell metabolic activity, proliferation, or apoptosis. Overall, these data suggest that LEAP2 can modulate pancreatic endocrine cell function under in vitro conditions, but further studies using standard glucose-stimulated insulin secretion protocols and in vivo models are required to define its physiological relevance.