Intestinal NUCB2/nesfatin-1 regulates hepatic glucose production via the MC4R-cAMP-GLP-1 pathway.

ABSTRACT: Communication of gut hormones with the central nervous system is important to regulate systemic glucose homeostasis, but the precise underlying mechanism involved remain little understood. Nesfatin-1, encoded by nucleobindin-2 (NUCB2), a potent anorexigenic peptide hormone, was found to be released from the gastrointestinal tract, but its specific function in this context remains unclear. Herein, we found that gut nesfatin-1 can sense nutrients such as glucose and lipids and subsequently decreases hepatic glucose production. Nesfatin-1 infusion in the small intestine of NUCB2-knockout rats reduced hepatic glucose production via a gut - brain - liver circuit. Mechanistically, NUCB2/nesfatin-1 interacted directly with melanocortin 4 receptor (MC4R) through its H-F-R domain and increased cycl

SUBMITTER: Geng S 

PROVIDER: S-EPMC11696497 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature