Intermittent administration of brain-derived neurotrophic factor ameliorates glucose metabolism in obese diabetic mice

We have previously shown that brain-derived neurotrophic factor (BDNF), a m ember of the neurotrophin family, interacts with the endocrine system in ob ese diabetic mice, and systemic peripheral administration of BDNF regulates glucose metabolism in this model. Results from the present study show that the hypoglycemic effect induced by 2 weeks' daily administration of BDNF ( 20 mg/kg/d) to db/db mice lasts for several weeks after treatment cessation , irrespective of food reduction. On the other hand, the antidiabetic agent , metformin had no lasting effect. This duration of the BDNF hypoglycemic a ction prompted us to examine the efficacy of BDNF intermittent administrati on on glucose metabolism. BDNF administered once or twice per week (70 mg/k g/wk) to db/db mice for 3 weeks significantly reduced blood glucose concent rations and hemoglobin A(1c) (HbA(1c)) as compared with ad libitum-fed phos phate-buffered saline (PBS)-treated and pair-fed PBS-treated groups. This s uggests that BDNF not only temporarily reduced blood glucose concentrations but also ameliorated systemic glucose balance in this obese diabetic mouse model during the experimental period. Our results indicate that BDNF could be a novel hypoglycemic agent with an exceptional ability to normalize glu cose metabolism even with treatment as infrequently as once per week. Copyr ight (C) 2000 by W.B. Saunders Company.