ANPEP and hyperinsulinemic hypoglycemia, familial, 4: Serum APN deficiency may contribute to insulin resistance in diabetes (Iwabu et al, 2010) and an APN receptor 1 and 2 agonist reduces plasma glucose in diabetic mice (Okada‐Iwabu et al, 2013), suggesting that APN may protect against hyperglycemia‐associated metabolic complications including retinal alterations.