Brain-derived neurotrophic factor (BDNF) and type 2 diabetes

The Centre of Inflammation and Metabolism, Department of Infectious Diseases, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
Diabetologia (Impact Factor: 6.67). 03/2007; 50(2):431-8. DOI: 10.1007/s00125-006-0537-4
Source: PubMed

ABSTRACT 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.
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.
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.
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.

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    • "However, further investigation into this phenomenon needs to be completed before a substantive conclusion is made. Furthermore, these findings support the hypotheses that BDNF is linked to multiple parameters of energy metabolism and homeostasis in diabetes (Krabbe et al. 2007; Yamanaka et al. 2008). Nakagawa et al. (2002) injected BDNF subcutaneously into STZinduced diabetic mice with or without insulin administration. "
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    ABSTRACT: Exercise is known to have beneficial effects on cognitive function. This effect is greatly favored by an exercise-induced increase in neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1), especially with high-intensity exercises (HIE). As a complication of type 1 diabetes (T1D), a cognitive decline may occur, mostly ascribed to hypoglycaemia and chronic hyperglycaemia. Therefore, the purpose of this study was to examine the effects of acute HIE on cognitive function and neurotrophins in T1D and matched controls. Ten trained T1D (8 males, 2 females) participants and their matched (by age, sex, fitness level) controls were evaluated on 2 occasions after familiarization: a maximal test to exhaustion and an HIE bout (10 intervals of 60 s at 90% of their maximal wattage followed by 60 s at 50 W). Cognitive tests and analyses of serum BDNF, IGF-1, and free insulin were performed before and after HIE and following 30 min of recovery. At baseline, cognitive performance was better in the controls compared with the T1D participants (p < 0.05). After exercise, no significant differences in cognitive performance were detected. BDNF levels were significantly higher and IGF-1 levels were significantly lower in T1D compared with the control group (p < 0.05) at all time points. Exercise increased BDNF and IGF-1 levels in a comparable percentage in both groups (p < 0.05). In conclusion, although resting levels of serum BDNF and IGF-1 were altered by T1D, comparable increasing effects on BDNF and IGF-1 in T1D and healthy participants were found. Therefore, regularly repeating acute HIE could be a promising strategy for brain health in T1D.
    Applied Physiology Nutrition and Metabolism 01/2015; 40(1). DOI:10.1139/apnm-2014-0098 · 2.34 Impact Factor
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    • "It is a nerve growth and positively contributes to neurogenesis, neurodegeneration, and hippocampal neural plasticity, and enhances memory and learning4). A lower than normal BDNF level has been observed among individuals with obesity and T2DM5), and this has been reported to bring about neuropsychosis, severe depression, and Alzheimer’s disease6), and has also recently been found to affect metabolism in the skeletal muscles6). "
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    ABSTRACT: [Purpose] The purpose of this study was to investigate the effects of 12 weeks regular aerobic exercise on brain-derived neurotrophic factor (BDNF) and inflammatory factors in juvenile obesity and type 2 diabetes mellitus (T2DM). Obesity and T2DM, typically common among adults, have recently become more prevalent in the Korean juvenile population, affecting not only their lipid profiles and oxidant stress levels, but also their BDNF and inflammatory factor levels. [Subjects] This study enrolled 26 juveniles (boys = 15, girls = 9) who were assigned to a control group (CG, n = 11), obesity group (OG, n = 8), or T2DM group (TG, n = 7). [Methods] The outcome of a 40-60-minute aerobic exercise session that took place three times per week for 12 weeks at a maximum oxygen intake (VO2max) of 50~60% was investigated. [Results] The exercise resulted in a significant reduction in the resting serum BDNF and TrkB levels (baseline) among juveniles in the OG and TG as compared to those in the CG. Additionally, the 12 weeks of regular aerobic exercise led to significant reductions in body weight, body fat percentage, and body mass index in the OG and a significant increase of VO2max in the OG and TG. However, no significant differences in serum NGF or inflammatory factors were found among the three groups. There was a significant increase in resting serum BDNF levels following the 12 weeks regular exercise only in the OG. [Conclusion] While 12 weeks of regular aerobic exercise had a positive effect on body composition, and increased BDNF levels of juveniles in the OG, it did not affect the inflammatory factor levels and had no effect on the TG.
    Journal of Physical Therapy Science 08/2014; 26(8):1199-204. DOI:10.1589/jpts.26.1199 · 0.39 Impact Factor
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    • "Down-regulation of the system has been proved to be a pathogenetic factor for depression, cardiovascular diseases, diabetes mellitus type 2 and for several components of metabolic syndrome. The activation of Sígma-1R signaling has emerged as a link between these pathologies [36,37]. "
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    ABSTRACT: BackgroundBlood platelets play an essential role in hemostasis, thrombosis and coagulation of blood. Beyond these classic functions their involvement in inflammatory, neoplastic and immune processes was also investigated. It is well known, that platelets have an armament of soluble molecules, factors, mediators, chemokines, cytokines and neurotransmitters in their granules, and have multiple adhesion molecules and receptors on their surface.MethodsSelected relevant literature and own views and experiences as clinical observations have been used.ResultsConsidering that platelets are indispensable in numerous homeostatic endocrine functions, it is reasonable to suppose that a platelet-associated regulatory system (PARS) may exist; internal or external triggers and/or stimuli may complement and connect regulatory pathways aimed towards target tissues and/or cells. The signal (PAF, or other tissue/cell specific factors) comes from the stimulated (by the e.g., hypophyseal hormones, bacteria, external factors, etc.) organs or cells, and activates platelets. Platelet activation means their aggregation, sludge formation, furthermore the release of the for-mentioned biologically very powerful factors, which can locally amplify and deepen the tissue specific cell reactions. If this process is impaired or inhibited for any reason, the specifically stimulated organ shows hypofunction. When PARS is upregulated, organ hyperfunction may occur that culminate in severe diseases.ConclusionBased on clinical and experimental evidences we propose that platelets modulate the function of hypothalamo-hypophyseal-ovarian system. Specifically, hypothalamic GnRH releases FSH from the anterior pituitary, which induces and stimulates follicular and oocyte maturation and steroid hormone secretion in the ovary. At the same time follicular cells enhance PAF production. Through these pathways activated platelets are accumulated in the follicular vessels surrounding the follicle and due to its released soluble molecules (factors, mediators, chemokines, cytokines, neurotransmitters) locally increase oocyte maturation and hormone secretion. Therefore we suggest that platelets are not only a small participant but may be the conductor or active mediator of this complex regulatory system which has several unrevealed mechanisms. In other words platelets are corpuscular messengers, or are more than a member of the family providing hemostasis.
    Journal of Ovarian Research 05/2014; 7(1):55. DOI:10.1186/1757-2215-7-55 · 2.43 Impact Factor
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