Endocrinological function of brain‐derived neurotrophic factor in diabetic mice

We previously found that chronic administration of Brain‐derived neurotrophic factor (BDNF) ameliorates glucose metabolism in diabetic animals. This demonstrated a new concept that a neurotrophic factor plays endocrinological function as well as neurological one. However, the mechanism underlying this new function is still poorly understood. In this study, we investigated the acute effects of BDNF on glucose metabolism and energy expenditure in diabetic mice. First, a single subcutaneous (s.c.) (70 mg/kg) or intracerebroventricular (i.c.v.)(0.3 mg/kg) injection of BDNF immediately enhanced insulin‐dependent hypoglycemic action in streptozotocin‐induced diabetic mice. In liver of this model, s.c. BDNF injection rapidly increased insulin‐stimulated tyrosine phosphorylation of insulin receptors (3.8 fold) and PI 3‐kinase activity (1.8 fold). Since i.c.v. injection reproduced the similar actions, BDNF may act on the central nervous system and rapidly modulate insulin signal transduction in peripheral tissues. Next, we examined the acute effects of BDNF on energy expenditure. The body temperatures of hyperphagic and obese diabetic C57BL/KsJ‐db/db mice dropped remarkably in 24 h after food removal. A single s.c. (20 mg/kg) or i.c.v. (0.125 mg/kg) injection of BDNF to db/db mice prevented the reduction of body temperature. BDNF increased the norepinephrine turnover and uncoupling protein‐1 mRNA levels in brown adipose tissue of db/db mice. Taken together, these suggest that BDNF has the direct action on the central nervous system and then regulates glucose and energy metabolisms possibly through modulating the autonomic nervous system in diabetic animals.