%0 Journal Article
%T Toll-like receptors TLR2 and TLR4 block the replication of pancreatic ¦Â cells in diet-induced obesity
%J -
%D 2019
%R https://doi.org/10.1038/s41590-019-0396-z
%X Consumption of a high-energy Western diet triggers mild adaptive ¦Â cell proliferation to compensate for peripheral insulin resistance; however, the underlying molecular mechanism remains unclear. In the present study we show that the toll-like receptors TLR2 and TLR4 inhibited the diet-induced replication of ¦Â cells in mice and humans. The combined, but not the individual, loss of TLR2 and TLR4 increased the replication of ¦Â cells, but not that of ¦Á cells, leading to enlarged ¦Â cell area and hyperinsulinemia in diet-induced obesity. Loss of TLR2 and TLR4 increased the nuclear abundance of the cell cycle regulators cyclin D2 and Cdk4 in a manner dependent on the signaling mediator Erk. These data reveal a regulatory mechanism controlling the proliferation of ¦Â cells in diet-induced obesity and suggest that selective targeting of the TLR2/TLR4 pathways may reverse ¦Â cell failure in patients with diabetes
%U https://www.nature.com/articles/s41590-019-0396-z