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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Overall dietary energy intake, particularly the consumption of simple sugars such as fructose, has been increasing steadily in Western societies, but the effects of such diets on the brain are poorly understood. Here, we used functional and structural assays to characterize the effects of excessive caloric intake on the hippocampus, a brain region important for learning and memory. Rats fed with a high-fat, high-glucose diet supplemented with high-fructose corn syrup showed alterations in energy and lipid metabolism similar to clinical diabetes, with elevated fasting glucose and increased cholesterol and triglycerides. Rats maintained on this diet for 8 months exhibited impaired spatial learning ability, reduced hippocampal dendritic spine density, and reduced long-term potentiation at Schaffer collateral--CA1 synapses. These changes occurred concurrently with reductions in levels of brain-derived neurotrophic factor in the hippocampus. We conclude that a high-calorie diet reduces hippocampal synaptic plasticity and impairs cognitive function, possibly through BDNF-mediated effects on dendritic spines.
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PMID:Diet-induced insulin resistance impairs hippocampal synaptic plasticity and cognition in middle-aged rats. 1865 34

Alzheimer's disease (AD) is a progressive neurodegenerative disease for which there are few therapeutic regimens that influence the underlying pathogenic phenotypes. However, of the currently available therapies, exercise training is considered to be one of the best candidates for amelioration of the pathological phenotypes of AD. Therefore, we directly investigated exercise training to determine whether it was able to ameliorate the molecular pathogenic phenotypes in the brain using a neuron-specific enolase (NSE)/Swedish mutation of amyloid precursor protein (APPsw) transgenic (Tg) mice as a novel AD model. To accomplish this, Non-Tg and NSE/ APPsw Tg mice were subjected to exercise on a treadmill for 16 weeks, after which their brains were evaluated to determine whether any changes in the pathological phenotype-related factors had occurred. The results indicated (i) that amyloid beta-42 (Abeta-42) peptides were significantly decreased in the NSE/APPsw Tg mice following exercise training; (ii) that exercise training inhibited the apoptotic biochemical cascades, including cytochrome c, caspase-9, caspase-3 and Bax; (iii) that the glucose transporter-1 (GLUT-1) and brain-derived neurotrophic factor (BDNF) proteins induced by exercise training protected the neurons from injury by inducing the concomitant expression of genes that encode proteins such as superoxide dismutase-1 (SOD-1), catalase and Bcl-2, which suppress oxidative stress and excitotoxic injury; (iv) that heat-shock protein-70 (HSP-70) and glucose-regulated protein-78 (GRP-78) were significantly increased in the exercise (EXE) group when compared to the sedentary (SED) group, and that these proteins may benefit the brain by making it more resistant to stress-induced neuron cell damage; (v) and that exercise training contributed to the restoration of normal levels of serum total cholesterol, insulin and glucose. Taken together, these results suggest that exercise training represents a practical therapeutic strategy for human subjects suffering from AD. Moreover, this training has the potential for use in new therapeutic strategies for the treatment of other chronic disease including diabetes, cardiovascular and Parkinson's disease.
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PMID:Exercise training acts as a therapeutic strategy for reduction of the pathogenic phenotypes for Alzheimer's disease in an NSE/APPsw-transgenic model. 1881 61

Obesity results from the interaction of genetic and environmental factors. To search for sequence variants that affect variation in two common measures of obesity, weight and body mass index (BMI), both of which are highly heritable, we performed a genome-wide association (GWA) study with 305,846 SNPs typed in 25,344 Icelandic, 2,998 Dutch, 1,890 European Americans and 1,160 African American subjects and combined the results with previously published results from the Diabetes Genetics Initiative (DGI) on 3,024 Scandinavians. We selected 43 variants in 19 regions for follow-up in 5,586 Danish individuals and compared the results to a genome-wide study on obesity-related traits from the GIANT consortium. In total, 29 variants, some correlated, in 11 chromosomal regions reached a genome-wide significance threshold of P < 1.6 x 10(-7). This includes previously identified variants close to or in the FTO, MC4R, BDNF and SH2B1 genes, in addition to variants at seven loci not previously connected with obesity.
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PMID:Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. 1907 60

Hypothalamic brain-derived neurotrophic factor (BDNF) is a key element in the regulation of energy balance. Here we investigated the therapeutic efficacy of BDNF by gene transfer in mouse models of obesity and diabetes. Gene transfer of BDNF led to marked weight loss and alleviation of obesity-associated insulin resistance. To facilitate clinical translation and ensure that BDNF protein expression was appropriately decreased as weight loss progressed, thus preventing cachexia, we developed a molecular autoregulatory system involving a single recombinant adeno-associated virus vector harboring two expression cassettes, one constitutively driving BDNF and the other driving a specific microRNA targeting BDNF. The microRNA element was controlled by a promoter (that controlling the Agrp gene encoding agouti-related peptide) responsive to BDNF-induced physiological changes. Hence, as body weight decreased and agouti-related protein is induced, microRNA expression was activated, inhibiting transgene expression. In contrast to the progressive weight loss associated with a nonregulated approach, this microRNA-approach led to a sustainable plateau of body weight after notable weight loss was achieved. This strategy mimics the body's endogenous physiological feedback mechanisms, thereby resetting the hypothalamic set point to reverse obesity and metabolic syndrome.
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PMID:Molecular therapy of obesity and diabetes by a physiological autoregulatory approach. 1927 Jul 10

Diabetes may adversely affect cognitive function, but the underlying mechanisms are unknown. To investigate whether manipulations that enhance neurotrophin levels will also restore neuronal structure and function in diabetes, we examined the effects of wheel running and dietary energy restriction on hippocampal neuron morphology and brain-derived neurotrophic factor (BDNF) levels in db/db mice, a model of insulin resistant diabetes. Running wheel activity, caloric restriction, or the combination of the two treatments increased levels of BDNF in the hippocampus of db/db mice. Enhancement of hippocampal BDNF was accompanied by increases in dendritic spine density on the secondary and tertiary dendrites of dentate granule neurons. These studies suggest that diabetes exerts detrimental effects on hippocampal structure, and that this state can be attenuated by increasing energy expenditure and decreasing energy intake.
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PMID:Voluntary exercise and caloric restriction enhance hippocampal dendritic spine density and BDNF levels in diabetic mice. 1928 Jun 61

Dietary restriction (DR) is known to have potential health benefits including enhanced resistance of neurons to excitotoxic, oxidative and metabolic insults, cancer, stress, diabetes, reduced morbidity, and increased life span. In the present study, we examined the effect of DR (alternate day feeding regimen) on neurogenesis, expression of immature neuronal marker polysialic acid neural cell adhesion molecule (PSA-NCAM) and neurotrophic factors from different brain regions such as subventricular zone (SVZ), subgranular zone (SGZ) of hippocampus, median eminence arcuate (ME-ARC) region of hypothalamus, and piriform cortex (PIR) of adult male rats and further challenged ad libitum fed (AL) and DR rats with pilocarpine to induce excitotoxic injury. The quantitative analysis of bromodeoxyuridine (BrdU) labeling revealed a significant increase in the proliferation rate of neuronal progenitor cells from discrete brain regions in DR rats with and without pilocarpine induced seizures as compared to AL rats. DR significantly enhanced the expression of PSA-NCAM and neurotrophic factors, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3). There was a marked reduction in neuronal cell death in SVZ and PIR cortex after pilocarpine administration in DR rats. These results add to the accumulating evidence that DR may be an effective intervention to enhance the resistance of brain to excitotoxic injury.
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PMID:Interactive effect of excitotoxic injury and dietary restriction on neurogenesis and neurotrophic factors in adult male rat brain. 1973 99

Recently, adipobiology (adiposcience) became a focus of numerous studies showing that the adipose tissue is the body's largest endocrine and paracrine organ producing multiple signaling proteins collectively designated adipokines; at present these include more than hundred proteins. However, studies on adipobiology of neurotrophins have recently emerged, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) being examples of adipose-derived neurotrophins. Here we present data showing that NGF and BDNF are expressed in both white and brown adipose tissue following experimental stress (in mice) and in type 1 diabetes (in rats). We suggest that both neurotrophic and metabotrophic potentials of NGF and BDNF may be involved in the molecular mechanism of stress and diabetes and consequently, in the pathogenesis of cardiometabolic diseases.
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PMID:Adipose tissue-derived nerve growth factor and brain-derived neurotrophic factor: results from experimental stress and diabetes. 1989 98

The circulating level of brain-derived neurotrophic factor (BDNF) is reduced in patients with major depression and type-2 diabetes. Because acute exercise increases BDNF production in the hippocampus and cerebral cortex, we hypothesized that endurance training would enhance the release of BDNF from the human brain as detected from arterial and internal jugular venous blood samples. In a randomized controlled study, 12 healthy sedentary males carried out 3 mo of endurance training (n = 7) or served as controls (n = 5). Before and after the intervention, blood samples were obtained at rest and during exercise. At baseline, the training group (58 + or - 106 ng x 100 g(-1) x min(-1), means + or - SD) and the control group (12 + or - 17 ng x 100 g(-1) x min(-1)) had a similar release of BDNF from the brain at rest. Three months of endurance training enhanced the resting release of BDNF to 206 + or - 108 ng x 100 g(-1) x min(-1) (P < 0.05), with no significant change in the control subjects, but there was no training-induced increase in the release of BDNF during exercise. Additionally, eight mice completed a 5-wk treadmill running training protocol that increased the BDNF mRNA expression in the hippocampus (4.5 + or - 1.6 vs. 1.4 + or - 1.1 mRNA/ssDNA; P < 0.05), but not in the cerebral cortex (4.0 + or - 1.4 vs. 4.6 + or - 1.4 mRNA/ssDNA) compared with untrained mice. The increased BDNF expression in the hippocampus and the enhanced release of BDNF from the human brain following training suggest that endurance training promotes brain health.
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PMID:Endurance training enhances BDNF release from the human brain. 1992 61

Diabetic retinopathy is characterized by pathological retinal neovascularization. Accumulating evidence has indicated that high levels of circulating endothelial progenitor cells (EPCs) are an important risk factor for neovascularization. Paradoxically, the reduction and dysfunction of circulating EPCs has been extensively reported in diabetic patients. We hypothesized that EPCs are differentially altered in the various vasculopathic complications of diabetes mellitus, exhibiting distinct behaviors in terms of angiogenic response to ischemia and growth factors and potentially playing a potent role in motivating vascular precursors to induce pathological neovascularization. Circulating levels of EPCs from diabetic retinopathy patients were analyzed by flow cytometry and by counting EPC colony-forming units, and serum levels of neurotrophic factors were measured by enzyme-linked immunosorbent assay. We found increased levels of nerve growth factor and brain-derived neurotrophic factor in the blood of diabetic retinopathy patients; this increase was correlated with the levels of circulating EPCs. In addition, we demonstrated that retinal cells released neurotrophic factors under hypoxic conditions to enhance EPC activity in vitro and to increase angiogenesis in a mouse ischemic hindlimb model. These results suggest that neurotrophic factors may induce neoangiogenesis through EPC activation, leading to the pathological retinal neovascularization. Thus, we propose that neovascularization in the ischemic retina might be regulated by overexpression of neurotrophic factors.
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PMID:Endothelial progenitor cells (EPCs) mobilized and activated by neurotrophic factors may contribute to pathologic neovascularization in diabetic retinopathy. 1994 24

The prevalence of metabolic syndrome as well as the occurrence of depressive disorder, which are both connected with increased risk of diabetes mellitus type 2 and cardiovascular diseases, is continually increasing worldwide. These disorders are interconnected at various levels; the genetic one seems to be promising. Contribution of genetic factors to the aetiopathogenesis of depressive disorder weighs within the range 40-50 %, whereas the genetic background for the manifestation of metabolic syndrome is more complicated. In this pilot study, we investigated the incidence of polymorphisms in several genes supposed to play a role in the development of both depressive disorder and metabolic syndrome such as brain-derived neurotrophic factor, methylenetetrahydrofolate reductase, tyrosine hydroxylase, and endothelial nitric oxide synthase. The entire group consisted of 42 patients with depressive disorder, 57 probands with metabolic syndrome and 41 control individuals. We found that genotype Met/Met of the Val66Met polymorphism of the brain-derived neurotrophic factor gene was positively associated with depressive disorder (P < 0.05), but we were not able to find any significant associations of both the depressive disorder and metabolic syndrome with the remaining polymorphisms studied (methylenetetrahydrofolate reductase 677CT, methylenetet rahydrofolate reductase 1298AC, endothelial nitric oxide synthase Glu298Asp, and tyrosine hydroxylase).
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PMID:Polymorphisms of genes for brain-derived neurotrophic factor, methylenetetrahydrofolate reductase, tyrosine hydroxylase, and endothelial nitric oxide synthase in depression and metabolic syndrome. 2016 78


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