PMID- 10868966
OWN - NLM
STAT- MEDLINE
DCOM- 20000713
LR  - 20190515
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 49
IP  - 3
DP  - 2000 Mar
TI  - Brain-derived neurotrophic factor regulates glucose metabolism by modulating 
      energy balance in diabetic mice.
PG  - 436-44
AB  - We previously reported that brain-derived neurotrophic factor (BDNF) regulates 
      both food intake and blood glucose metabolism in rodent obese diabetic models 
      such as C57BL/KsJ-lepr(db)/lepr(db) (db/db) mice. To elucidate the effect of BDNF 
      on glucose metabolism, we designed a novel pellet pair-feeding apparatus to 
      eliminate the effect of appetite alteration on glucose metabolism. The apparatus 
      was used to synchronize food intake precisely between BDNF-treated and 
      vehicle-treated db/db mice. It was shown using this pellet pair-feeding apparatus 
      that BDNF administered daily (20 mg x kg(-1) x day(-1)) to db/db mice 
      significantly lowered blood glucose compared with pellet pair-fed db/db mice. To 
      evaluate the effect of BDNF on insulin action, we used streptozotocin-induced 
      type 1 diabetic mice. In this case, BDNF did not lower blood glucose 
      concentration but rather enhanced the hypoglycemic action of insulin. In 
      hyperglycemic db/db mice, pancreatic insulin content was reduced and glucagon 
      content was increased compared with normoglycemic db/m mice. BDNF administered to 
      db/db mice significantly restored both pancreatic insulin and glucagon content. 
      Histological observations of aldehyde-fuchsin staining and immunostaining with 
      anti-insulin indicated that insulin-positive pancreatic beta-cells were 
      extensively regranulated by BDNF administration. We also studied the effect of 
      BDNF on KK mice, normoglycemic animals with impaired glucose tolerance. In these 
      mice, BDNF administration improved insulin resistance in the oral glucose 
      tolerance test. To elucidate how blood glucose was metabolized in BDNF-treated 
      animals, we investigated the effect of BDNF on the energy metabolism of db/db 
      mice. Body temperature and oxygen consumption of the pellet pair-fed 
      vehicle-treated mice were remarkably lower than the ad libitum-fed 
      vehicle-treated mice. Daily BDNF administration for 3 weeks completely 
      ameliorated both of the reductions. Finally, to clarify its action mechanism, the 
      effect of intracerebroventricular administration of BDNF on db/db mice was 
      examined. Here, a small dose of BDNF was found to be effective in lowering blood 
      glucose concentration. This indicates that BDNF regulates glucose metabolism by 
      acting directly on the brain.
FAU - Nakagawa, T
AU  - Nakagawa T
AD  - Sumitomo Pharmaceuticals Research Center, Discovery Research Laboratories II, 
      Osaka, Japan.
FAU - Tsuchida, A
AU  - Tsuchida A
FAU - Itakura, Y
AU  - Itakura Y
FAU - Nonomura, T
AU  - Nonomura T
FAU - Ono, M
AU  - Ono M
FAU - Hirota, F
AU  - Hirota F
FAU - Inoue, T
AU  - Inoue T
FAU - Nakayama, C
AU  - Nakayama C
FAU - Taiji, M
AU  - Taiji M
FAU - Noguchi, H
AU  - Noguchi H
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Blood Glucose)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Blood Glucose/analysis
MH  - Body Temperature/drug effects
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Diabetes Mellitus/genetics/metabolism/pathology/*physiopathology
MH  - Diabetes Mellitus, Experimental/blood
MH  - Eating/drug effects
MH  - Energy Metabolism/*drug effects
MH  - Food Deprivation/physiology
MH  - Glucose/*metabolism
MH  - Injections, Intraventricular
MH  - Islets of Langerhans/pathology
MH  - Mice
MH  - Mice, Inbred C57BL/genetics
MH  - Mice, Mutant Strains
MH  - Pancreas/drug effects/pathology
EDAT- 2000/06/27 11:00
MHDA- 2000/07/15 11:00
CRDT- 2000/06/27 11:00
PHST- 2000/06/27 11:00 [pubmed]
PHST- 2000/07/15 11:00 [medline]
PHST- 2000/06/27 11:00 [entrez]
AID - 10.2337/diabetes.49.3.436 [doi]
PST - ppublish
SO  - Diabetes. 2000 Mar;49(3):436-44. doi: 10.2337/diabetes.49.3.436.