IRS1 and Hyperglycemia: Although chronic therapy with metformin fails to achieve recovery from hyperglycemia, a key feature of diabetes in middle‐aged diabetic mice, it improves hippocampal‐dependent spatial memory functions accompanied by increased phosphorylation of adenosine monophosphate‐activated protein kinase (AMPK), atypical protein kinase C ζ (aPKC ζ), and insulin receptor substrate 1 (IRS1) at selective serine residues in the hippocampus.