PMID- 23274899
OWN - NLM
STAT- MEDLINE
DCOM- 20130628
LR  - 20211021
IS  - 1939-327X (Electronic)
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 62
IP  - 5
DP  - 2013 May
TI  - BDNF action in the brain attenuates diabetic hyperglycemia via 
      insulin-independent inhibition of hepatic glucose production.
PG  - 1512-8
LID - 10.2337/db12-0837 [doi]
AB  - Recent evidence suggests that central leptin administration fully normalizes 
      hyperglycemia in a rodent model of uncontrolled insulin-deficient diabetes by 
      reducing hepatic glucose production (HGP) and by increasing glucose uptake. The 
      current studies were undertaken to determine whether brain-derived neurotrophic 
      factor (BDNF) action in the brain lowers blood glucose in uncontrolled 
      insulin-deficient diabetes and to investigate the mechanisms mediating this 
      effect. Adult male rats implanted with cannulas to either the lateral cerebral 
      ventricle or the ventromedial hypothalamic nucleus (VMN) received either vehicle 
      or streptozotocin to induce uncontrolled insulin-deficient diabetes. Three days 
      later, animals received daily intracerebroventricular or intra-VMN injections of 
      either BDNF or its vehicle. We found that repeated daily intracerebroventricular 
      administration of BDNF attenuated diabetic hyperglycemia independent of changes 
      in food intake. Instead, using tracer dilution techniques during a basal clamp, 
      we found that BDNF lowered blood glucose levels by potently suppressing HGP, 
      without affecting tissue glucose uptake, an effect associated with normalization 
      of both plasma glucagon levels and hepatic expression of gluconeogenic genes. 
      Moreover, BDNF microinjection directly into the VMN also lowered fasting blood 
      glucose levels in uncontrolled insulin-deficient diabetes, but this effect was 
      modest compared with intracerebroventricular administration. We conclude that 
      central nervous system BDNF attenuates diabetic hyperglycemia via an 
      insulin-independent mechanism. This action of BDNF likely involves the VMN and is 
      associated with inhibition of glucagon secretion and a decrease in the rate of 
      HGP.
FAU - Meek, Thomas H
AU  - Meek TH
AD  - Diabetes and Obesity Center of Excellence, Department of Medicine, University of 
      Washington, Seattle, Washington, USA.
FAU - Wisse, Brent E
AU  - Wisse BE
FAU - Thaler, Joshua P
AU  - Thaler JP
FAU - Guyenet, Stephan J
AU  - Guyenet SJ
FAU - Matsen, Miles E
AU  - Matsen ME
FAU - Fischer, Jonathan D
AU  - Fischer JD
FAU - Taborsky, Gerald J Jr
AU  - Taborsky GJ Jr
FAU - Schwartz, Michael W
AU  - Schwartz MW
FAU - Morton, Gregory J
AU  - Morton GJ
LA  - eng
GR  - T32 HL007028/HL/NHLBI NIH HHS/United States
GR  - T32 DK007247/DK/NIDDK NIH HHS/United States
GR  - T32 DK0007247/DK/NIDDK NIH HHS/United States
GR  - DK050154-13/DK/NIDDK NIH HHS/United States
GR  - R01 DK089056/DK/NIDDK NIH HHS/United States
GR  - K08 DK088872/DK/NIDDK NIH HHS/United States
GR  - DK089053/DK/NIDDK NIH HHS/United States
GR  - R01 DK050154/DK/NIDDK NIH HHS/United States
GR  - P30 DK035816/DK/NIDDK NIH HHS/United States
GR  - DK083042/DK/NIDDK NIH HHS/United States
GR  - DK035816/DK/NIDDK NIH HHS/United States
GR  - F32 DK097859/DK/NIDDK NIH HHS/United States
GR  - R01 DK090320/DK/NIDDK NIH HHS/United States
GR  - R01 DK083042/DK/NIDDK NIH HHS/United States
GR  - R56 DK050154/DK/NIDDK NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20121228
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Insulin)
RN  - 9007-92-5 (Glucagon)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
CIN - Diabetes. 2013 May;62(5):1367-8. PMID: 23613551
MH  - Animals
MH  - Behavior, Animal/drug effects
MH  - Biological Transport/drug effects
MH  - Brain-Derived Neurotrophic Factor/administration & dosage/*metabolism
MH  - Diabetes Mellitus, Type 1/blood/drug therapy/*metabolism
MH  - Feeding Behavior/drug effects
MH  - Glucagon/blood/metabolism
MH  - *Gluconeogenesis/drug effects
MH  - Glucose/metabolism
MH  - Hyperglycemia/*prevention & control
MH  - Hypoglycemic Agents/therapeutic use
MH  - Injections, Intraventricular
MH  - Insulin/therapeutic use
MH  - Lateral Ventricles/drug effects/metabolism
MH  - Liver/drug effects/*metabolism
MH  - Male
MH  - Neurons/drug effects/*metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Ventromedial Hypothalamic Nucleus/drug effects/*metabolism
PMC - PMC3636618
EDAT- 2013/01/01 06:00
MHDA- 2013/07/03 06:00
PMCR- 2014/05/01
CRDT- 2013/01/01 06:00
PHST- 2013/01/01 06:00 [entrez]
PHST- 2013/01/01 06:00 [pubmed]
PHST- 2013/07/03 06:00 [medline]
PHST- 2014/05/01 00:00 [pmc-release]
AID - db12-0837 [pii]
AID - 0837 [pii]
AID - 10.2337/db12-0837 [doi]
PST - ppublish
SO  - Diabetes. 2013 May;62(5):1512-8. doi: 10.2337/db12-0837. Epub 2012 Dec 28.