Interestingly, Timp4−/− HFD-fed mice are not protected from obesity-induced glucose intolerance despite their decreased body fat, plasma TG and fatty acids, which have been linked to glucose intolerance through impairing insulin signaling; however, Timp4−/−-HFD mice are protected from hyperinsulinemia and accumulation of intramuscular TG. This evidence concerns the gene INS and Hyperinsulinemia.