Moreover, systemic administration of FGF21 improves insulin sensitivity and relieves hyperinsulinemia in ob/ob, db/db mice, diet-induced obese mice and diabetic monkeys,3, 4, 5, 6, 7 which are consistent with our data that loss of FGF21 induces insulin resistance and hyperinsulinemia. The gene discussed is INS; the disease is hyperinsulinism.