Brain-derived neurotrophic factor (BDNF) and type 2 diabetes.
OBJECTIVE
Decreased levels of brain-derived neurotrophic factor (BDNF) have been implicated in the pathogenesis of Alzheimer's disease and depression. These disorders are associated with type 2 diabetes, and animal models suggest that BDNF plays a role in insulin resistance. We therefore explored whether BDNF plays a role in human glucose metabolism.


METHODS
We included (Study 1) 233 humans divided into four groups depending on presence or absence of type 2 diabetes and presence or absence of obesity; and (Study 2) seven healthy volunteers who underwent both a hyperglycaemic and a hyperinsulinaemic-euglycaemic clamp.


RESULTS
Plasma levels of BDNF in Study 1 were decreased in humans with type 2 diabetes independently of obesity. Plasma BDNF was inversely associated with fasting plasma glucose, but not with insulin. No association was found between the BDNF G196A (Val66Met) polymorphism and diabetes or obesity. In Study 2 an output of BDNF from the human brain was detected at basal conditions. This output was inhibited when blood glucose levels were elevated. In contrast, when plasma insulin was increased while maintaining normal blood glucose, the cerebral output of BDNF was not inhibited, indicating that high levels of glucose, but not insulin, inhibit the output of BDNF from the human brain.


CONCLUSIONS
Low levels of BDNF accompany impaired glucose metabolism. Decreased BDNF may be a pathogenetic factor involved not only in dementia and depression, but also in type 2 diabetes, potentially explaining the clustering of these conditions in epidemiological studies.
Krabbe
K S
KS
The Centre of Inflammation and Metabolism, Department of Infectious Diseases, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. karen.krabbe@dadlnet.dk
Nielsen
A R
AR
Krogh-Madsen
R
R
Plomgaard
P
P
Rasmussen
P
P
Erikstrup
C
C
Fischer
C P
CP
Lindegaard
B
B
Petersen
A M W
AM
Taudorf
S
S
Secher
N H
NH
Pilegaard
H
H
Bruunsgaard
H
H
Pedersen
B K
BK
D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood / Q000235:genetics / Q000502:physiology*; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood; D003430:Cross-Sectional Studies; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000453:epidemiology / Q000235:genetics; D003925:Diabetic Angiopathies / Q000097:blood; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D008297:Male; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values
D001786:Blood Glucose; D019208:Brain-Derived Neurotrophic Factor; D007328:Insulin; D002097:C-Reactive Protein; D004247:DNA