Brain-derived neurotrophic factor improves blood glucose control and alleviates fasting hyperglycemia in C57BLKS-Leprdb/leprdb mice

被引:145
作者
Tonra, JR
Ono, M
Liu, XC
Garcia, K
Jackson, C
Yancopoulos, GD
Wiegand, SJ
Wong, V
机构
[1] Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA
[2] Sumitomo Pharmaceut Res Ctr, Discovery Labs 2, Osaka, Japan
关键词
D O I
10.2337/diabetes.48.3.588
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 HbA(1c) 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 out-put 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.
引用
收藏
页码:588 / 594
页数:7
相关论文
共 29 条
[1]   FATTY LIVER HEPATITIS AND CIRRHOSIS IN OBESE PATIENTS [J].
ADLER, M ;
SCHAFFNER, F .
AMERICAN JOURNAL OF MEDICINE, 1979, 67 (05) :811-816
[2]   Synaptic innervation density is regulated by neuron-derived BDNF [J].
Causing, CG ;
Gloster, A ;
Aloyz, R ;
Bamji, SX ;
Chang, E ;
Fawcett, J ;
Kuchel, G ;
Miller, FD .
NEURON, 1997, 18 (02) :257-267
[3]   HEPATIC-METABOLISM OF GENETICALLY DIABETIC (DB-DB) MICE .1. CARBOHYDRATE-METABOLISM [J].
CHAN, TM ;
YOUNG, KM ;
HUTSON, NJ ;
BRUMLEY, FT ;
EXTON, JH .
AMERICAN JOURNAL OF PHYSIOLOGY, 1975, 229 (06) :1702-1712
[4]  
Coleman D L, 1967, Diabetologia, V3, P238, DOI 10.1007/BF01222201
[5]   Glycohaemoglobin: a crucial measurement in modern diabetes management - Progress towards standardisation and improved precision of measurement [J].
Colman, PG ;
Goodall, GI ;
GarciaWebb, P ;
Williams, PF ;
Dunlop, ME .
MEDICAL JOURNAL OF AUSTRALIA, 1997, 167 (02) :96-98
[6]   THE TRIUMVIRATE - BETA-CELL, MUSCLE, LIVER - A COLLUSION RESPONSIBLE FOR NIDDM [J].
DEFRONZO, RA .
DIABETES, 1988, 37 (06) :667-687
[7]   THE NEUROTROPHINS BDNF, NT-3, AND NGF DISPLAY DISTINCT PATTERNS OF RETROGRADE AXONAL-TRANSPORT IN PERIPHERAL AND CENTRAL NEURONS [J].
DISTEFANO, PS ;
FRIEDMAN, B ;
RADZIEJEWSKI, C ;
ALEXANDER, C ;
BOLAND, P ;
SCHICK, CM ;
LINDSAY, RM ;
WIEGAND, SJ .
NEURON, 1992, 8 (05) :983-993
[8]   GLUCOSE REGULATION IN NON-INSULIN-DEPENDENT DIABETES-MELLITUS - INTERACTION BETWEEN PANCREATIC-ISLETS AND THE LIVER [J].
HALTER, JB ;
WARD, WK ;
PORTE, D ;
BEST, JD ;
PFEIFER, MA .
AMERICAN JOURNAL OF MEDICINE, 1985, 79 (2B) :6-12
[9]  
HEMS DA, 1980, PHYSIOL REV, V60, P1
[10]  
HENRY RJ, 1960, AM J CLIN PATHOL, V34, P381