INS and Hyperglycemia: Intriguingly, although glucose metabolism was impaired in both mutants, increased 4-HNE in aldh3a1 mutants disrupted the pancreas leading to hyperglycemia and retinal vessel alterations, while increased ACR in akr1a1a mutants led to insulin resistance and hallmarks of diabetic retinopathy and diabetic nephropathy in adult animals [10,11].