PMID- 11380073
OWN - NLM
STAT- MEDLINE
DCOM- 20011011
LR  - 20131121
IS  - 0012-186X (Print)
IS  - 0012-186X (Linking)
VI  - 44
IP  - 5
DP  - 2001 May
TI  - The effects of brain-derived neurotrophic factor on insulin signal transduction 
      in the liver of diabetic mice.
PG  - 555-66
AB  - AIM/HYPOTHESIS: We previously reported that repeated subcutaneous or 
      intracerebroventricular injection of brain-derived neurotrophic factor (BDNF) 
      reduces blood glucose concentrations in obese diabetic C57BL/KsJ-db/db mice. In 
      this study, we assessed the effects of BDNF on insulin action in peripheral 
      tissues of diabetic mice. METHODS: First, brain-derived neurotrophic factor (20 
      mg/kg) was subcutaneously given to male db/db mice for 14 days and then the 
      insulin-stimulated tyrosine phosphorylation of insulin receptors and 
      insulin-stimulated phosphatidylinositol (PI) 3-kinase activity in peripheral 
      tissues was assessed. Second, we examined the effects of a single subcutaneous or 
      intracerebroventricular brain-derived neurotrophic factor injection on insulin 
      responsiveness in liver and skeletal muscle of streptozotocin (STZ)-induced 
      diabetic mice. Third, the effects of brain-derived neurothrophic factor on 
      insulin action were also examined in cultured cells. RESULTS: Repeated injection 
      of BDNF to db/db mice for 14 days enhanced insulin-stimulated tyrosine 
      phosphorylation of insulin receptors in liver and insulin-stimulated PI 3-kinase 
      activity in liver, skeletal muscle and interscapular brown adipose tissue. We 
      then examined the rapid effect of BDNF on insulin signalling in vivo. A single 
      subcutaneous or intracerebroventricular injection of BDNF rapidly increased 
      insulin-stimulated tyrosine phosphorylation of insulin receptors and PI 3-kinase 
      activity in liver of STZ-mice. No direct effect of brain-derived neurothrophic 
      factor was observed on insulin signalling in primary cultured hepatocytes, L6 
      muscle cells or 3T3-L1 adipocytes. Brain-derived neurothrophic factor did not 
      affect either glucose uptake or gluconeogenesis in these cells. 
      CONCLUSION/INTERPRETATION: These data indicate that brain-derived neurothrophic 
      factor rapidly enhances insulin signal transduction in liver and shows 
      hypoglycaemic action in diabetic mice.
FAU - Tsuchida, A
AU  - Tsuchida A
AD  - Sumitomo Pharmaceuticals, Osaka, Japan.
FAU - Nakagawa, T
AU  - Nakagawa T
FAU - Itakura, Y
AU  - Itakura Y
FAU - Ichihara, J
AU  - Ichihara J
FAU - Ogawa, W
AU  - Ogawa W
FAU - Kasuga, M
AU  - Kasuga M
FAU - Taiji, M
AU  - Taiji M
FAU - Noguchi, H
AU  - Noguchi H
LA  - eng
PT  - Journal Article
PL  - Germany
TA  - Diabetologia
JT  - Diabetologia
JID - 0006777
RN  - 0 (Blood Glucose)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Insulin)
RN  - 0 (Recombinant Proteins)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.10.1 (Receptor, Insulin)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - 3T3 Cells
MH  - Adipose Tissue, Brown/drug effects/metabolism
MH  - Animals
MH  - Blood Glucose/drug effects/metabolism
MH  - Brain-Derived Neurotrophic Factor/administration & dosage/*pharmacology
MH  - Cell Line
MH  - Cerebral Ventricles/drug effects
MH  - Diabetes Mellitus, Experimental/*physiopathology
MH  - Gluconeogenesis/drug effects
MH  - Glucose/metabolism
MH  - Hepatocytes/drug effects/physiology
MH  - Humans
MH  - Injections, Intraventricular
MH  - Insulin/*pharmacology/physiology
MH  - Kinetics
MH  - Liver/drug effects/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Mutant Strains
MH  - Muscle, Skeletal/drug effects/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Receptor, Insulin/drug effects/*metabolism
MH  - Recombinant Proteins/administration & dosage/pharmacology
MH  - Signal Transduction/drug effects/physiology
EDAT- 2001/05/31 10:00
MHDA- 2001/10/12 10:01
CRDT- 2001/05/31 10:00
PHST- 2001/05/31 10:00 [pubmed]
PHST- 2001/10/12 10:01 [medline]
PHST- 2001/05/31 10:00 [entrez]
AID - 10.1007/s001250051661 [doi]
PST - ppublish
SO  - Diabetologia. 2001 May;44(5):555-66. doi: 10.1007/s001250051661.