Brain-derived neurotrophic factor improves blood glucose control and alleviates fasting hyperglycemia in C57BLKS-Lepr(db)/lepr(db) mice

• Published in: Diabetes (New York, N.Y.) Vol. 48; no. 3; pp. 588 - 594
• Main Authors: Tonra, J R, Ono, M, Liu, X, Garcia, K, Jackson, C, Yancopoulos, G D, Wiegand, S J, Wong, V
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01.03.1999
• Subjects: Animals; Blood Glucose - drug effects; Blood Glucose - metabolism; Brain-Derived Neurotrophic Factor - pharmacology; Brain-Derived Neurotrophic Factor - therapeutic use; Diabetes Mellitus - blood; Diabetes Mellitus - drug therapy; Diabetes Mellitus - metabolism; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Fasting; Glucose Tolerance Test; Glycated Hemoglobin A - analysis; Heterozygote; Hyperglycemia - prevention & control; Liver - drug effects; Liver - metabolism; Liver Glycogen - metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Obesity; Time Factors
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.48.3.588

Brain-derived neurotrophic factor improves blood glucose control and alleviates fasting hyperglycemia in C57BLKS-Lepr(db)/lepr(db) mice. J R Tonra , M Ono , X Liu , K Garcia , C Jackson , G D Yancopoulos , S J Wiegand and V Wong Regeneron Pharmaceuticals, Tarrytown, New York 10591, USA. Abstract Systemic administration of brain-derived neurotrophic factor (BDNF) decreases nonfasted blood glucose in obese, non-insulin-dependent diabetic C57BLKS-Lepr(db)/lepr(db) (db/db) mice, with a concomitant decrease in body weight. By measuring percent HbA1c in BDNF-treated and pair-fed animals, we show that the effects of BDNF on nonfasted blood glucose levels are not caused by decreased food intake but reflect a significant improvement in blood glucose control. Furthermore, once established, this effect can persist for weeks after cessation of BDNF treatment. Oral glucose tolerance tests were performed to examine the effects of BDNF on blood glucose control in the fasted state and after an oral glucose challenge. BDNF treatment normalized fasting blood glucose from initially hyperglycemic levels and also showed evidence for beneficial, although less marked, effects on the ability to remove exogenous glucose from blood. One means to lower fasting blood glucose is to reduce the glucose output of peripheral tissues that normally play a part in the maintenance of fasting hyperglycemia. Because the liver is the major endogenous source of glucose in blood during fasting, and because hepatic weight and glucose output are increased in type 2 diabetes, we evaluated the effects of BDNF on liver tissue. BDNF reduced the hepatomegaly present in db/db mice, in association with reduced liver glycogen and reduced liver enzyme activity in serum, supporting the possible involvement of liver tissue in the mechanism of action for BDNF.