PMID- 16979397
OWN - NLM
STAT- MEDLINE
DCOM- 20061031
LR  - 20111117
IS  - 0026-0495 (Print)
IS  - 0026-0495 (Linking)
VI  - 55
IP  - 10
DP  - 2006 Oct
TI  - Protective effect of brain-derived neurotrophic factor on pancreatic islets in 
      obese diabetic mice.
PG  - 1286-92
AB  - We have previously demonstrated that brain-derived neurotrophic factor (BDNF) 
      ameliorates glucose metabolism and energy expenditure in obese diabetic db/db 
      mice. In the present study, the effect of BDNF treatment on pancreatic islets of 
      db/db mice was examined, using vehicle-treated pair-fed db/db mice as controls. 
      Brain-derived neurotrophic factor (10 mg/kg) or vehicle was subcutaneously 
      administered to male db/db mice for 4 weeks. The food intake of vehicle-treated 
      db/db mice was restricted and precisely synchronized with that of BDNF-treated 
      db/db mice using a pellet pair-feeding apparatus because BDNF decreases food 
      intake in hyperphagic mice. Repetitive administration of BDNF significantly 
      lowered the blood glucose concentration compared with pair-fed vehicle-treated 
      db/db mice. The pancreatic insulin and glucagon concentrations were measured in 
      db/db mice to evaluate the effect of BDNF on the pancreas. Although the insulin 
      concentration in the pancreas of pair-fed vehicle-treated db/db mice was lower 
      than in nondiabetic control +m/+m mice, it was higher in BDNF-treated db/db mice 
      than in vehicle-treated pair-fed db/db mice and comparable to the concentration 
      in +m/+m mice. The glucagon concentration in the pancreas of vehicle-treated 
      pair-fed db/db mice was higher than in +m/+m mice, and BDNF partially decreased 
      the glucagon concentration in the pancreas of db/db mice compared with vehicle. 
      Histologic analyses of pancreatic sections were performed to characterize the 
      mechanism through which BDNF modulates the hormonal concentration in the pancreas 
      of db/db mice. Although there were no significant differences in the number and 
      total area of islets between the BDNF- and vehicle-treated groups, immunostaining 
      with an anti-insulin antibody indicated that the islet beta-cell area in 
      BDNF-treated db/db mice was larger than that in vehicle-treated pair-fed db/db 
      mice. Furthermore, immunostaining with an antiglucagon antibody indicated that 
      BDNF normalized the delocalization of non-beta cells in islets of db/db mice. 
      Electron microscopic images of beta cells indicated a decrease in secretory 
      granules in vehicle-treated pair-fed db/db mice; this change was reversed in 
      BDNF-treated db/db mice and reached a level comparable to that found in +m/+m 
      mice. These findings suggest that BDNF prevents exhaustion of the pancreas in 
      diabetic mice by maintaining the histologic cellular organization of beta cells 
      and non-beta cells in pancreatic islets and restoring the level of 
      insulin-secreting granules in beta cells.
FAU - Yamanaka, Mitsugu
AU  - Yamanaka M
AD  - Discovery Pharmacology Group I, Pharmacology Research Laboratories, Drug Research 
      Division, Dainippon Sumitomo Pharma Co., Ltd., Chuo-ku, Tokyo 541-0045, Japan.
FAU - Itakura, Yasushi
AU  - Itakura Y
FAU - Inoue, Tadashi
AU  - Inoue T
FAU - Tsuchida, Atsushi
AU  - Tsuchida A
FAU - Nakagawa, Tsutomu
AU  - Nakagawa T
FAU - Noguchi, Hiroshi
AU  - Noguchi H
FAU - Taiji, Mutsuo
AU  - Taiji M
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Metabolism
JT  - Metabolism: clinical and experimental
JID - 0375267
RN  - 0 (Blood Glucose)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Insulin)
RN  - 0 (Recombinant Proteins)
RN  - 9007-92-5 (Glucagon)
SB  - IM
MH  - Animals
MH  - Blood Glucose/metabolism
MH  - Brain-Derived Neurotrophic Factor/*pharmacology/therapeutic use
MH  - Diabetes Mellitus/*genetics/*pathology
MH  - Glucagon/blood/metabolism
MH  - Immunohistochemistry
MH  - Insulin/blood/metabolism
MH  - Insulin-Secreting Cells/drug effects/metabolism/ultrastructure
MH  - Islets of Langerhans/*drug effects/*pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Obese
MH  - Microscopy, Electron
MH  - Obesity/*drug therapy/*pathology
MH  - Pancreas/metabolism/pathology
MH  - Recombinant Proteins/pharmacology/therapeutic use
EDAT- 2006/09/19 09:00
MHDA- 2006/11/01 09:00
CRDT- 2006/09/19 09:00
PHST- 2006/02/23 00:00 [received]
PHST- 2006/04/26 00:00 [accepted]
PHST- 2006/09/19 09:00 [pubmed]
PHST- 2006/11/01 09:00 [medline]
PHST- 2006/09/19 09:00 [entrez]
AID - S0026-0495(06)00159-4 [pii]
AID - 10.1016/j.metabol.2006.04.017 [doi]
PST - ppublish
SO  - Metabolism. 2006 Oct;55(10):1286-92. doi: 10.1016/j.metabol.2006.04.017.