To obtain the information on subjects of this review article, I have searched articles providing molecular mechanisms of insulin resistance onset by using the following terms: insulin resistance, interstitial fluid pH, type 2 diabetes mellitus, amyloid-β, Alzheimer’s disease, β- and γ-secretases, weak organic acids, SMCT1 (Na+-coupled monocarboxylate transporter 1), pH capacity, acidosis, ketone bodies, lactic acid and diet therapies in PubMed and Google Scholar. Here, INS is linked to diabetes mellitus.