Acute glucose load induced islet β cells dysfunction in TLR4 dependent manner in male mice

Recent studies highlighted the significance of chronic inflammation, which is mediated in part by toll-like receptors 4 (TLR4), in islet β cell dysfunction by high-glucose exposure. However, about it is unclear whether islet β cell dysfunction in response to high glucose is associated with TLR4. This investigation was designed to address the effect of TLR4 deficiency on insulin secretion in mice in response to acute intravenous glucose load. Hyperglycemic clamp was used to impair insulin secretion, and intraperitoneal glucose tolerance test was carried out to analyze insulin secretion function of islet β cells. Our results showed that TLR4 deficiency repressed insulin secretion impairment in response to acute intravenous glucose load. Compared to wild-type mice, TLR4^-/- mice did not exhibit increase of IL-1β and TNF-α level in plasma and pancreatic tissue in response to acute intravenous load of high glucose. However, recombinant IL-1β or TNF-α administration restored insulin secretion impairment induced by high glucose in TLR4^-/- mice. Taken together, our results demonstrated that TLR4 activation and subsequent IL-1β and TNF-α production contribute to islet β cell dysfunction in mice in response to acute intravenous load of high glucose, which may provide a theoretical basis for diabetes complication improvement by physical exercise.