Acute activation of Gq-signaling in islet macrophages inhibits β-cell insulin secretion through AMPK-sphingolipid axis.

ABSTRACT: Obesity-associated inflammation disrupts pancreatic β-cell function, but the immune-derived signals that directly regulate insulin secretion remain incompletely defined. Here, we identify myeloid Gq signaling as a critical immunometabolic node that links macrophage activation to β-cell dysfunction. For the first time, we employed a chemogenetic approach (DREADDs) to selectively and temporally activate Gq-coupled GPCR signaling in myeloid cells to examine its effect on islet function. Our findings reveal that acute Gq activation in islet-resident macrophages impaired glucose-stimulated insulin secretion, uncovering a previously unrecognized immune-endocrine axis. Conversely, myeloid-specific Gαq deletion improves systemic glucose homeostasis, underscoring the physiological relevance of this

SUBMITTER: Singh S 

PROVIDER: S-EPMC12636625 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature