Hormonal
GLP-1 receptor activation suppresses glucagon secretion primarily through an indirect mechanism involving somatostatin release from delta-cells, rather than direct action on alpha-cells.
GLP-1 drugs help control blood sugar not just by boosting insulin, but by suppressing glucagon (a hormone that raises blood sugar). This suppression happens indirectly by stimulating other cells (delta-cells) to release somatostatin, which then inhibits glucagon. This dual action makes GLP-1 drugs effective for lowering blood glucose.
Collectively, these findings present strong evidence for the indirect theory of GLP-1 mediated glucagon inhibition... GLP-1 mediates its glucagonostatic effect indirectly through stimulation of somatostatin secretion from pancreatic delta-cells, that express functional GLP-1R... administration of GLP-1 suppressed glucagon secretion, with this inhibitory effect annulled in the presence of a specific somatostatin receptor 2 (SSTR2) antagonist
Why this rating
Based on mechanistic studies in perfused pancreas models and knockout mice, cited as 'strong evidence' for the indirect theory.
Source
Metabolic responses and benefits of glucagon‐like peptide‐1 (GLP‐1) receptor ligands
Neil Tanday et al. · British Journal of Pharmacology · 2021
DOI 10.1111/bph.15485
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