AIMS/HYPOTHESIS: 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. SUBJECTS AND 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/ INTERPRETATION: 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.
AIMS/HYPOTHESIS: 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 humanglucose metabolism. SUBJECTS AND 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 BDNFG196A (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/ INTERPRETATION: 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.
Authors: M Ono; J Ichihara; T Nonomura; Y Itakura; M Taiji; C Nakayama; H Noguchi Journal: Biochem Biophys Res Commun Date: 1997-09-18 Impact factor: 3.575
Authors: T Nakagawa; A Tsuchida; Y Itakura; T Nonomura; M Ono; F Hirota; T Inoue; C Nakayama; M Taiji; H Noguchi Journal: Diabetes Date: 2000-03 Impact factor: 9.461
Authors: Michael F Egan; Masami Kojima; Joseph H Callicott; Terry E Goldberg; Bhaskar S Kolachana; Alessandro Bertolino; Eugene Zaitsev; Bert Gold; David Goldman; Michael Dean; Bai Lu; Daniel R Weinberger Journal: Cell Date: 2003-01-24 Impact factor: 41.582
Authors: Olga Carlson; Bronwen Martin; Kim S Stote; Erin Golden; Stuart Maudsley; Samer S Najjar; Luigi Ferrucci; Donald K Ingram; Dan L Longo; William V Rumpler; David J Baer; Josephine Egan; Mark P Mattson Journal: Metabolism Date: 2007-12 Impact factor: 8.694
Authors: F Bernhard; K Landgraf; N Klöting; A Berthold; P Büttner; D Friebe; W Kiess; P Kovacs; M Blüher; A Körner Journal: Diabetologia Date: 2012-11-16 Impact factor: 10.122
Authors: Tomas Hajek; Margaret Hahn; Claire Slaney; Julie Garnham; Joshua Green; Martina Růzicková; Peter Zvolský; Martin Alda Journal: Bipolar Disord Date: 2008-06 Impact factor: 6.744
Authors: Jerzy A Zoladz; Michał Śmigielski; Joanna Majerczak; Łukasz R Nowak; Justyna Zapart-Bukowska; Olgierd Smoleński; Jan Kulpa; Krzysztof Duda; Joanna Drzewińska; Grzegorz Bartosz Journal: Neurochem Res Date: 2012-08-19 Impact factor: 3.996