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

The size and frequency of meals are fundamental aspects of nutrition that can have profound effects on the health and longevity of laboratory animals. In humans, excessive energy intake is associated with increased incidence of cardiovascular disease, diabetes, and certain cancers and is a major cause of disability and death in industrialized countries. On the other hand, the influence of meal frequency on human health and longevity is unclear. Both caloric (energy) restriction (CR) and reduced meal frequency/intermittent fasting can suppress the development of various diseases and can increase life span in rodents by mechanisms involving reduced oxidative damage and increased stress resistance. Many of the beneficial effects of CR and fasting appear to be mediated by the nervous system. For example, intermittent fasting results in increased production of brain-derived neurotrophic factor (BDNF), which increases the resistance of neurons in the brain to dysfunction and degeneration in animal models of neurodegenerative disorders; BDNF signaling may also mediate beneficial effects of intermittent fasting on glucose regulation and cardiovascular function. A better understanding of the neurobiological mechanisms by which meal size and frequency affect human health may lead to novel approaches for disease prevention and treatment.
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PMID:Energy intake, meal frequency, and health: a neurobiological perspective. 1601 67

During brain aging and progression of Alzheimer's disease, the levels of Abeta and proinflammatory cytokines accumulate very early in the pathogenic process prior to any major degenerative changes. Accumulation of these molecules may impair with signal transduction pathways critical for neuronal health. Neurotrophin signaling is a critical mechanism involved in synaptic plasticity, learning and memory and neuronal health. We have recently shown that exposure to low levels of Abeta impairs BDNF trkB signal transduction, suppressing the Ras/ERK, and the PI3-K/Akt pathways but not the PLCgamma pathway. As a result, downstream regulation of gene expression and neuronal viability are impaired. Recently, we have found that at least three agents--Abeta, TNFalpha, Il-1beta--suppress TrkB signaling and act via a common and novel mechanism. These factors all regulate the docking proteins (e.g., IRS and Shc) that link the activated Trk receptor to downstream effectors. While this is a novel mechanism underlying regulation of Trk signaling, such a mechanism has been identified for the insulin/IGF-1 receptor in the presence of proinflammatory cytokines and is one of the mechanisms for insulin/IGF-resistance, which is a key risk factor for type II diabetes (1). We suggest that accumulation of AB and proinflammatory cytokines during aging generates in the brain a "neurotrophin resistance" state that places the brain at risk for cognitive decline and dementia.
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PMID:The role of neurotrophins in brain aging: a perspective in honor of Regino Perez-Polo. 1618 22

Streptozotocin is well known inducer of experimental diabetes mellitus when injected peripherally. However, when administered intracerebroventricular, streptozotocin showed a whole spectrum of specific biochemical and behavioural alterations with regard to cognitive functions, feeding, nociception, brain glucose metabolism, neurotransmission and oxidative stress, without producing arterial hyperglycaemia, similarly to Alzheimer's disease. In order to reveal the mechanism of action of neurodegeneration in streptozotocin rat model we investigated the expression of several genes involved in inflammation, oxidative stress, growth- and transcription-factors in the cortex, striatum and cerebellum, using real-time quantitative RT-PCR. Genes such as GDNF, BDNF and integrin-alpha-M were up-regulated, while immediate-early-gene-transcription-factor NGF-IB and metallothionein-1/2 were down-regulated in the cortex of streptozotocin-treated rats. Conversely, NGF-IB, GDNF and BDNF mRNA expression did not alter in the striatum and cerebellum. However, integrin alpha-M and metallothionein-1/2 expressions decreased significantly in the striatum and increased in the cerebellum. These gene changes may provide an insight into the cascade of physiological abnormalities following the inhibition of neuronal insulin signal transduction. Additionally, similarities to neuronal cell death in sporadic Alzheimer's disease may become apparent.
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PMID:Gene expression alterations in brain areas of intracerebroventricular streptozotocin treated rat. 1691 36

The neurotrophin brain-derived neurotrophic factor (BDNF) inhibits food intake, and rodent models of BDNF disruption all exhibit increased food intake and obesity, as well as hyperactivity. We report an 8-year-old girl with hyperphagia and severe obesity, impaired cognitive function, and hyperactivity who harbored a de novo chromosomal inversion, 46,XX,inv(11)(p13p15.3), a region encompassing the BDNF gene. We have identified the proximal inversion breakpoint that lies 850 kb telomeric of the 5' end of the BDNF gene. The patient's genomic DNA was heterozygous for a common coding polymorphism in BDNF, but monoallelic expression was seen in peripheral lymphocytes. Serum concentration of BDNF protein was reduced compared with age- and BMI-matched subjects. Haploinsufficiency for BDNF was associated with increased ad libitum food intake, severe early-onset obesity, hyperactivity, and cognitive impairment. These findings provide direct evidence for the role of the neurotrophin BDNF in human energy homeostasis, as well as in cognitive function, memory, and behavior.
Diabetes 2006 Dec
PMID:Hyperphagia, severe obesity, impaired cognitive function, and hyperactivity associated with functional loss of one copy of the brain-derived neurotrophic factor (BDNF) gene. 1713 Apr 81

Neuropathic pain is often a consequence of nerve injury through surgery, bone compression, diabetes or infection. This type of pain can be so severe that even light touching can be intensely painful. Unfortunately, this state is generally resistant to currently available treatments. There is abundant evidence that activated microglia are a key player for causing the pain and ATP receptors expressed in microglia have an important role to activate microglia. In this review, we summarize the role of microglia and ATP receptors in neuropathic pain signalling. The activated microglia express P2X4 after nerve injury, which can be stimulated by endogenous ATP, resulting in the release of BDNF which is one of key molecules involving in neuropathic pain. The microglia also express many molecules that were reported to be connected in the pain. Understanding the key roles of these ATP receptors in microglia may lead to new strategies for the management of intractable chronic pain.
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PMID:[Involvement of microglia in neuropathic pain signalling]. 1766 45

Several epidemiological and clinical studies have indicated that the prevalence of psychiatric disorders is higher in diabetic patients than in the general population. In the present studies, we examined the behavioral changes in streptozotocin-induced diabetic rats, and investigated the effects of physical and psychological stress on the hippocampal BDNF levels and on the serotonin 2A (5-HT(2A)) receptor-mediated wet-dog shake responses. The streptozotocin (60 mg/kg, i.p.)-induced diabetes had no significant effects on the immobility time in the forced swim test or on locomotor activity in the open-field test. Moreover, there was no significant difference in the wet-dog shake responses induced by DOI, a 5-HT(2A) receptor agonist, between nondiabetic and diabetic rats. Five-day exposure to physical (electric footshock) and psychological (non-footshock) stress had no significant effect on the hippocampal BDNF level in diabetic or nondiabetic rats. The 2 types of stress had no significant effect on the DOI-induced wet-dog shake responses in nondiabetic rats. In diabetic rats, the repeated exposure to physical stress markedly increased the DOI-induced wet-dog shake responses, but the repeated exposure to psychological stress had no effect. These results suggest that exposure to physical stress augmented the susceptibility to the wet-dog shake responses to 5-HT(2A) receptor stimulation in streptozotocin-induced diabetic rats.
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PMID:Effects of physical and psychological stress on 5-HT2A receptor-mediated wet-dog shake responses in streptozotocin-induced diabetic rats. 1772 9

Neuropathic pain resulting from nerve injury or from diseases such as diabetes, HIV AIDS or cancer, that damage the peripheral nerves, can be agonizing, persistent over long periods, and, unfortunately, is often resistant to known pain-killers. The P2X receptors, of which seven subtypes (P2X1-P2X7) have been cloned, are a family of ligand-gated cation channels activated by extracellular ATP and have important roles in regulating neuronal and glial functions in the nervous system. Recent advances in our understanding of the mechanisms underlying neuropathic pain have been made by defining important roles of P2X4 receptors and spinal microglia in the pathogenesis of neuropathic pain. Within the spinal dorsal horn, peripheral nerve injury leads to a progressive series of changes in microglia including morphological hypertrophy of the cell body and proliferation that are considered indicative of activation. Furthermore, P2X4 receptors that which are upregulated in activated microglia, have been found to be essential molecular mediators. The activation of P2X4 receptors releases brain-derived neurotrophic factor from microglia; this mediates the signaling from microglia to neurons, which in turn leads to pain hypersensitivity. We expect that understanding the key roles of these molecules in spinal microglia may lead to new strategies for the management of neuropathic pain.
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PMID:[Neuropathic pain and ATP receptors in spinal microglia]. 1788 77

Neurogenic erectile dysfunction (NED) caused by pelvic floor surgeries/radiation therapies and associated with Parkinsons disease and diabetes remains a challenging healthcare issue. To facilitate NED research we have developed in vitro and in vivo experimental models. The in vitro model comprises the isolation, culture and treatment of rat major pelvic ganglia (MPG), which then produce outgrowing neurites whose length and molecular composition are indicative of the neurotrophic effect of the treatment agent. Through this approach we have confirmed that the brain-derived neurotrophic factor (BDNF) promotes nerve regeneration by activating the JAK/STAT signaling pathway. This has been further established by our in vivo model, which involves the transection or cruch of cavernous nerves and treatment with BDNF.
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PMID:[The in vitro and in vivo experimental models of erectile nerve regeneration]. 1828 49

We previously demonstrated that repetitive administration of brain-derived neurotrophic factor (BDNF) ameliorates glucose metabolism and energy expenditure in obese diabetic db/db mice. However, we have not evaluated in detail the effect of single or intermittent BDNF administration on glucose metabolism in a diabetic animal model. The objectives of this study were to examine the dose-response effect and dosing interval of BDNF administration in db/db mice and to evaluate the effect of intermittent BDNF administration on pancreatic function in db/db mice. We evaluated the dose-response effect of BDNF by single administration in db/db mice. First, single administration of BDNF greater than 70 mg/kg significantly reduced blood glucose concentration one day after administered, and the BDNF effect was maintained for 6 d. Next, the effects of BDNF administered twice a week at 4, 10, 25, and 62.5 mg/kg on blood glucose concentration, and the effects of BDNF administered once a week at 10, 20, 30, 50, and 70 mg/kg on blood glucose concentration were examined in db/db mice. In the intermittent treatment studies, BDNF dose-dependently ameliorated glucose metabolism by not only the twice-a-week administration but also the once-a-week administration. Lastly, because BDNF reduces the food intake of obese hyperphagic diabetic mice, the effects of BDNF administered once or twice a week on the blood glucose concentration and plasma and pancreatic insulin concentrations in db/db mice were compared with those of the vehicle under pair-fed conditions. Under pair-fed conditions, the intermittent administration of BDNF (25 mg/kg, twice a week, or 50 mg/kg, once a week) significantly reduced the blood glucose concentration and increased the plasma and pancreatic insulin concentrations compared with those in the pair-fed vehicle-treated db/db mice. This indicates that the prolonged hypoglycemic effect of BDNF is not simply due to the reduction of food intake. In conclusion, we demonstrated that the intermittent administration of BDNF ameliorates glucose metabolism and prevents pancreatic exhaustion in obese diabetic mice. These findings indicate that BDNF may have potential as a unique hypoglycemic agent for the treatment of diabetes at a fundamental level with good patient compliance.
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PMID:Intermittent administration of brain-derived neurotrophic factor (BDNF) ameliorates glucose metabolism and prevents pancreatic exhaustion in diabetic mice. 1849 57

We previously reported that peripheral injection of brain-derived neurotrophic factor (BDNF) exhibits hypophagic and hypoglycemic effects in obese hyperglycemic animals, indicating its antiobesity and antidiabetic effects. Since previous studies were focused on the effect of BDNF on overt diabetic animals with severe hyperglycemia, there was no evidence whether BDNF is effective or not for the development of diabetes in prediabetic animal models. Therefore, we evaluated the effect of BDNF on preventing the development of diabetes in db/db mice. First, we characterized age-related changes in the pathophysiology of diabetes in db/db mice. We chose 8 week-old db/db mice as the early diabetic stage (early intervention study) and 4 week-old db/db mice as the prediabetic stage (prevention study). Next, we examined the effects of BDNF on the progression of diabetes in early diabetic db/db mice. In the early intervention study using 8 week-old db/db mice, intermittent treatment with BDNF prevented the deterioration in hyperglycemia. Lastly, we examined the preventive effects of BDNF on the development of diabetes in prediabetic db/db mice. In the prevention study using 4 week-old db/db mice, treatment with BDNF prevented the age-related increase in blood glucose concentration. These results showed for the first time that BDNF prevents the development of diabetes in prediabetic db/db mice.
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PMID:Brain-derived neurotrophic factor (BDNF) prevents the development of diabetes in prediabetic mice. 1861 48


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