 It is possible that protease inhibitors can cause a decrease in insulin-stimulated tyrosine phosphorylation of IRS-1, representing inhibition of early steps in insulin signaling.Decreased adiponectin secretion and induced expression of interleukin-6 associated with HIV protease inhibitors may also contribute to inhibition of insulin-stimulated glucose uptake.Protease inhibitors were designed to mimic the transition state of the protease's actual substrates.