Consequently, we hypothesized that the minimal impact of HMGB1 knockdown on glucose levels in mice during periods of normoglycemia (i.e., low cellular stress) can be ascribed to the insufficient stress levels to evoke the substantial role that HMGB1 overexpression typically plays in exacerbating DM and hyperglycemia phenotypes. This evidence concerns the gene HMGB1 and diabetes mellitus.