Metabolic Homeostasis (metabolic + homeostasi)

Distribution by Scientific Domains

Selected Abstracts

CB1 receptors: emerging evidence for central and peripheral mechanisms that regulate energy balance, metabolism, and cardiovascular health

Daniela Cota
Abstract Insulin resistance, dyslipidaemia and obesity are the major cardiometabolic risk factors contributing to the development of type 2 diabetes and cardiovascular disease (CVD). Owing to the increasing prevalence of obesity, type 2 diabetes, and CVD, new and effective pharmacologic therapies are urgently needed. In this regard, the endogenous cannabinoid system (ECS), a neuromodulatory system involved in the regulation of various aspects of energy balance and eating behaviour through central and peripheral mechanisms, may present the potential to meet this need. In the central nervous system (CNS), cannabinoid type 1 (CB1) receptors and their respective ligands, the endocannabinoids, have a significant role in the modulation of food intake and motivation to consume palatable food. CB1 receptors have also been found in organs involved in the regulation of metabolic homeostasis, such as liver, white adipose tissue, muscle and pancreas. Dysregulation of the ECS has been associated with the development of dyslipidaemia, glucose intolerance, and obesity, and CB1 receptor blockade may have a role in ameliorating these metabolic abnormalities. Thus, pharmacologic options targeting the ECS may provide a novel, effective approach to the prevention and management of CVD, type 2 diabetes and obesity. Copyright 2007 John Wiley & Sons, Ltd. [source]

The Space Mission MIR'97: operational aspects

R. Ewald
Background A German astronaut visited the MIR space station between 10 February and 2 March 1997. Together with his Russian colleagues, he conducted a series of scientific investigations before, during and after his stay aboard the MIR station. Research performed during this flight was part of a global space life sciences programme and focused on metabolic homeostasis, fluid balance, calcium homeostasis and cardiovascular regulatory mechanisms. The main goal of the scientific experiments was to use this mission as a milestone to establish international networks of scientific collaboration using space research as a tool for focused research in respective fields. Thus, in most cases the results obtained from the astronaut complemented a series of results obtained on ground and from other flights. In other cases, they extended previous results and opened new fields for future research. Participants Human space flight with astronauts serving as operators and at the same time as test subjects is very complex. Many people, including mission control, a science management team, medical operations, ethics committees and a medical board, participated to harmonize the different requirements, thus making a maximal scientific outcome possible. Conclusion In summary, this space mission may be seen as a model for focused long-term multidisciplinary international research, and demonstrates that space medicine is no longer adventure but science. [source]

Comprehensive studies of cognitive impairment of the elderly with type 2 diabetes

Takashi Sakurai
Type 2 diabetes mellitus is associated with cognitive dysfunction and increases the risk of dementia for the elderly. The aim of the study presented here was to provide a brief review of how disturbance of glucose and metabolic homeostasis may be implicated in the cognitive decline of patients with type 2 diabetes. Several risk factors such as nutrition, cerebrovascular disorders and the neurotoxic effects of hyperglycemia may combine for the formation of mechanisms of cognitive decline in the diabetic elderly. It should be noted that cognitive deficits of diabetes are accompanied by neuroradiological changes in the brain, so that cognitive dysfunction both with and without brain structural changes may overlap during cognitive decline of the diabetic elderly. Recently, we conducted two studies to explore, by means of brain imaging, hierarchical relationships among clinical profiles of diabetes, cognitive function, white matter hyperintensity and brain atrophy. The results suggested that subcortical brain atrophy and hyperintensity constitute predictors of the rate of progression of cognitive dysfunction in the diabetic elderly, while cortical atrophy is associated with high diastolic blood pressure and lower HbA1c. These hypotheses may explain in part the underlying mechanisms of cognitive impairment in the diabetic elderly. Prospective intervention studies are needed, however, to clarify the mechanism of cognitive dysfunction of the diabetic elderly and what the targets are for preventive measures. [source]

Oxidative stress and longevity in Caenorhabditis elegans as mediated by SKN-1

AGING CELL, Issue 3 2009
Sang-Kyu Park
Summary Oxidative stress has been hypothesized to play a role in normal aging. The response to oxidative stress is regulated by the SKN-1 transcription factor, which also is necessary for intestinal development in Caenorhabditis elegans. Almost a thousand genes including the antioxidant and heat-shock responses, as well as genes responsible for xenobiotic detoxification were induced by the oxidative stress which was found using transcriptome analysis. There were also 392 down-regulated genes including many involved in metabolic homeostasis, organismal development, and reproduction. Many of these oxidative stress-induced transcriptional changes are dependent on SKN-1 action; the induction of the heat-shock response is not. When RNAi to inhibit genes was used, most had no effect on either resistance to oxidative stress or longevity; however two SKN-1-dependent genes, nlp-7 and cup-4, that were up-regulated by oxidative stress were found to be required for resistance to oxidative stress and for normal lifespan. nlp-7 encodes a neuropeptide-like protein, expressed in neurons, while cup-4 encodes a coelomocyte-specific, ligand-gated ion channel. RNAi of nlp-7 or cup-4 increased sensitivity to oxidative stress and reduced lifespan. Among down-regulated genes, only inhibition of ent-1, a nucleoside transporter, led to increased resistance to oxidative stress; inhibition had no effect on lifespan. In contrast, RNAi of nhx-2, a Na+/H+ exchanger, extended lifespan significantly without affecting sensitivity to oxidative stress. These findings showed that a transcriptional shift from growth and maintenance towards the activation of cellular defense mechanisms was caused by the oxidative stress; many of these transcriptional alterations are SKN-1 dependent. [source]

Opioids and opiates: analgesia with cardiovascular, haemodynamic and immune implications in critical illness

Abstract. Traumatic injury, surgical interventions and sepsis are amongst some of the clinical conditions that result in marked activation of neuroendocrine and opiate responses aimed at restoring haemodynamic and metabolic homeostasis. The central activation of the neuroendocrine and opiate systems, known collectively as the stress response, is elicited by diverse physical stressor conditions, including ischaemia, glucopenia and inflammation. The role of the hypothalamic,pituitary,adrenal axis and sympathetic nervous system in counterregulation of haemodynamic and metabolic alterations has been studied extensively. However, that of the endogenous opiates/opioid system is still unclear. In addition to activation of the opiate receptor through the endogenous release of opioids, pharmacotherapy with opiate receptor agonists is frequently used for sedation and analgesia of injured, septic and critically ill patients. How this affects the haemodynamic, cardiovascular, metabolic and immune responses is poorly understood. The variety of opiate receptor types, their specificity and ubiquitous location both in the central nervous system and in the periphery adds additional complicating factors to the clear understanding of their contribution to the stress response to the various physical perturbations. This review aims at discussing scientific evidence gathered from preclinical studies on the role of endogenous opioids as well as those administered as pharmacological agents on the host cardiovascular, neuroendocrine, metabolic and immune response mechanisms critical for survival from injury in perspective with clinical observations that provide parallel assessment of relevant outcome measures. When possible, the clinical relevance and corresponding scenarios where this evidence can be integrated into our understanding of the clinical implications of opiate effects will be examined. Overall, the scientific basis to enhance clinical judgment and expectations when using opioid sedation and analgesia in the management of the injured, septic or postsurgical patient will be discussed. [source]

Adaptability and selectivity of human peroxisome proliferator-activated receptor (PPAR) pan agonists revealed from crystal structures

Takuji Oyama
Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear hormone receptor family, which is defined as transcriptional factors that are activated by the binding of ligands to their ligand-binding domains (LBDs). Although the three PPAR subtypes display different tissue distribution patterns and distinct pharmacological profiles, they all are essentially related to fatty-acid and glucose metabolism. Since the PPARs share similar three-dimensional structures within the LBDs, synthetic ligands which simultaneously activate two or all of the PPARs could be potent candidates in terms of drugs for the treatment of abnormal metabolic homeostasis. The structures of several PPAR LBDs were determined in complex with synthetic ligands, derivatives of 3-(4-alkoxyphenyl)propanoic acid, which exhibit unique agonistic activities. The PPAR, and PPAR, LBDs were complexed with the same pan agonist, TIPP-703, which activates all three PPARs and their crystal structures were determined. The two LBD,ligand complex structures revealed how the pan agonist is adapted to the similar, but significantly different, ligand-binding pockets of the PPARs. The structures of the PPAR, LBD in complex with an ,/,-selective ligand, TIPP-401, and with a related ,-specific ligand, TIPP-204, were also determined. The comparison between the two PPAR, complexes revealed how each ligand exhibits either a `dual selective' or `single specific' binding mode. [source]

Metabolic effects of static magnetic fields on streptococcus pyogenes

A.C. Morrow
Abstract This study aimed to develop a simple experimental system utilising bacterial cells to investigate the dose responses resulting from exposures to static magnetic flux densities ranging from 0.05 to 0.5 T on viability, bacterial metabolism and levels of DNA damage in Streptococcus pyogenes. Exposure of S. pyogenes to a field of 0.3 T at 24 C under anaerobic conditions resulted in a significant (P,<,0.05) decrease in growth rate, with an increased mean generation time of 199,,6 min compared to the control cells at 165,,6 min (P,<,0.05). Conversely, exposure to magnetic fields of 0.5 T significantly accelerated the growth rate at 24 C compared to control cells, with a decreased mean generation time of 147,,4 min (P,<,0.05). The patterns of metabolite release from cells incubated in phosphate buffered saline (PBS) at 24 C and exposed to different magnetic flux densities (0.05,0.5 T) were significantly (P,<,0.05) altered, compared to non-exposed controls. Concentrations of metabolites, with the exception of aspartic acid (r,=,0.44), were not linearly correlated with magnetic flux density, with all other r,<,0.20. Instead, "window" effects were observed, with 0.25,0.3 T eliciting the maximal release of the majority of metabolites, suggesting that magnetic fields of these strengths had significant impacts on metabolic homeostasis in S. pyogenes. The exposure of cells to 0.3 T was also found to significantly reduce the yield of 8-hydroxyguanine in extracted DNA compared to controls, suggesting some possible anti-oxidant protection to S. pyogenes at this field strength. Bioelectromagnetics 28:439,445, 2007. 2007 Wiley-Liss, Inc. [source]

Endocrine fibroblast growth factors as regulators of metabolic homeostasis

BIOFACTORS, Issue 1 2009
Hiroshi Kurosu
Abstract Endocrine fibroblast growth factors (FGFs) function as hormones that maintain specific metabolic states by controlling homeostasis of bile acid, glucose, fatty acid, phosphate, and vitamin D. Endocrine FGFs exert their biological activity through a common design of coreceptor system consisting of the Klotho gene family of transmembrane proteins and cognate FGF receptors. Moreover, expression of endocrine FGFs is regulated by nuclear receptors whose lipophilic ligands are generated under the control of these hormones in the target organs. Thus, novel endocrine axes have emerged that regulate diverse metabolic processes through feedback loops composed of the FGF, Klotho, FGF receptor, and nuclear receptor gene families. This review summarizes the role of Klotho family proteins in the regulation of metabolic activity and expression of the endocrine FGFs. 2009 International Union of Biochemistry and Molecular Biology, Inc. [source]

Serum concentrations and tissue expression of a novel endocrine regulator fibroblast growth factor-21 in patients with type 2 diabetes and obesity

M. Mraz
Summary Objective, Fibroblast growth factor-21 (FGF21) is a novel endocrine and paracrine regulator of metabolic homeostasis. The aim of our study was to measure its serum concentrations in patients with obesity, obesity and type 2 diabetes mellitus (T2DM) and healthy subjects (C), and to assess the changes of its circulating levels and mRNA expression after dietary and pharmacological interventions. Design, We measured biochemical parameters, serum FGF21, adiponectin, leptin and insulin levels by commercial ELISA and RIA kits, and mRNA expression in the liver, subcutaneous and visceral fat by RT PCR in 26 obese patients, 11 T2DM patients and 32 control subjects. The interventions were acute hyperinsulinaemia during isoglycaemic,hyperinsulinaemic clamp, very low calorie diet (VLCD) and 3 months treatment with PPAR-, agonist fenofibrate. Results, Baseline serum FGF21 levels were significantly higher in both obese and T2DM patients relative to healthy controls. FGF21 levels in obesity did not significantly differ from T2DM group. Both 3 weeks of VLCD and 3 months of fenofibrate treatment significantly increased FGF21 levels. FGF21 mRNA expression in visceral fat was twofold higher in obesity relative to C group, while it did not differ in subcutaneous fat. VLCD significantly increased FGF21 mRNA expression in subcutaneous fat of obesity. 3-h hyperinsulinaemia during the clamp increased FGF21 levels in T2DM but not in C group. Conclusion, An increase in FGF21 levels after VLCD and fenofibrate treatment may contribute to positive metabolic effect of these interventions and suggests the possibility of direct positive metabolic effects of FGF21 in humans. [source]