β-cell Jagged1 is sufficient but not necessary for islet Notch activity and insulin secretory defects in obese mice.

ABSTRACT:

Objective

Notch signaling, re-activated in β cells from obese mice and causal to β cell dysfunction, is determined in part by transmembrane ligand availability in a neighboring cell. We hypothesized that β cell expression of Jagged1 determines the maladaptive Notch response and resultant insulin secretory defects in obese mice.

Methods

We assessed expression of Notch pathway components in high-fat diet-fed (HFD) or leptin receptor-deficient (db/db) mice, and performed single-cell RNA sequencing (scRNA-Seq) in islets from patients with and without type 2 diabetes (T2D). We generated and performed glucose tolerance testing in inducible, β cell-specific Jagged1 gain-of- and loss-of-function mice. We also tested effects of monoclonal neutralizing antibodies to Jagged1 in glucose

SUBMITTER: Suda N 

PROVIDER: S-EPMC10877406 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature