The requirement for insulin to mediate the hypoglycemic effect of peripheral BDNF was demonstrated in streptozotocin-induced type 1 diabetic mice, which had no reduction in blood glucose levels after BDNF treatment alone, but showed an increased hypoglycemic action of insulin when co-administered with BDNF (Nakagawa et al., 2000). The gene discussed is INS; the disease is type 1 diabetes mellitus.