Although we demonstrated that female MTKO mice that were fed a HFD became obese and developed hyperleptinemia, they did not exhibit higher blood glucose or insulin levels compared with wild type mice.[16] Chen et al. recently reported that MT transgenic mice showed impaired glucose-stimulated insulin secretion, which promoted the development of diabetes.[46] This information suggests that MT expression negatively regulates glucose metabolism/insulin signaling and that MT deficiency enhances insulin sensitivity. This evidence concerns the gene INS and diabetes mellitus.