Highglucose administration induces glucose intolerance in mice: A critical role of tolllike receptor 4

Abstract

Glucose converted from a diet has been considered a highrisk factor of type 2 diabetes mellitus (T2DM). However, it is not clear how it increases the risk of T2DM. Here, we investigated the effect of highglucose administration on glucose tolerence in wild type and tolllike receptor 4 (TLR4) knockout mice. Mice were intragastrically administered with highglucose. The level of fasting blood glucose, insulin and intraperitoneal glucose tolerance were measured, and insulinogenic index and HOMAIR were calculated at 1 week. To understand mechanism of glucose action, we also assessed blood glucose, glucagonlike peptide1 and inflammatory cytokines levels at different time windows following highglucose load. Our results show that 20 g/kg glucose load leads to glucose tolerance impairment and insulin resistance in wildtype mice. Following 20 g/kg glucose load, the levels of plasma interlukin6 (IL6) and tumor necrosis factorα (TNFα) increased significantly in wildtype mice, but not in TLR4 knockout mice. Moreover, 20 g/kg glucose load also impaired glucoseinduced GLP1 secretion in wildtype and TLR4 knockout mice. Our results indicate that high glucose load leads to glucose intolerance with insulin resistance through impairment of GLP1 secretion, increase of blood glucose levels via activating TLR4 and increasing levels of IL6 and TNFα in mice.