Liraglutide increases islet Ca²⁺ oscillation frequency and insulin secretion by activating hyperpolarization-activated cyclic nucleotide-gated channels.

ABSTRACT:

Aim

To determine whether hyperpolarization-activated cyclic nucleotide-gated (HCN) channels impact glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) modulation of islet Ca²⁺ handling and insulin secretion.

Methods

The impact of liraglutide (GLP-1 analogue) on islet Ca²⁺ handling, HCN currents and insulin secretion was monitored with fluorescence microscopy, electrophysiology and enzyme immunoassays, respectively. Furthermore, liraglutide-mediated β-to-δ-cell cross-communication was assessed following selective ablation of either mouse islet δ or β cells.

Results

Liraglutide increased β-cell Ca²⁺ oscillation frequency in mouse and human islets under stimulatory glucose conditions. This was dependent in part on liraglutide activation of

SUBMITTER: Zaborska KE 

PROVIDER: S-EPMC9843726 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature