Toll-like receptor 4 is necessary for glucose-dependent glucagon-like peptide-1 secretion in male mice.

Lipopolysaccharide (LPS), a natural toll-like receptor 4 (TLR4) ligand, can induce the secretion of glucagon-like peptide-1 (GLP-1) in both animal models and humans consistent with the notion that TLR4 may influence physiological process of GLP-1 secretion. Here, we explored the possible role of TLR4 in the process of glucose-dependent GLP-1 secretion. Wild-type and TLR4 knockout mice were used to observe GLP-1 expression and secretion, as well as the cytokines tumor necrosis factor α (TNF-α), interleukin-6 (IL-6) levels in plasma and ileum after glucose load. TLR4 deficient mice also were given an injection of TNF-α and IL-6, respectively, to confirm the key role of TLR4-mediated inflammatory cytokines in the process of glucose-induced GLP-1 secretion. We found that the TLR4 deficiency impaired the glucose-induced GLP-1 release and prevented an increase in IL-6 and TNF-α levels in plasma and ileum following glucose stimulation. Importantly, injection of TLR4 deficient mice with either TNF-α and IL-6 partly restored the glucose-induced secretion of GLP-1. In conclusion, the production of pro-inflammatory cytokines downstream of TLR4 promotes glucose-dependent GLP-1 secretion from intestinal L-cells in mice.