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Metabolic Signals (metabolic + signal)
Selected AbstractsThe mechanisms that underlie glucose sensing during hypoglycaemia in diabetesDIABETIC MEDICINE, Issue 5 2008R. McCrimmon Abstract Hypoglycaemia is a frequent and greatly feared side-effect of insulin therapy, and a major obstacle to achieving near-normal glucose control. This review will focus on the more recent developments in our understanding of the mechanisms that underlie the sensing of hypoglycaemia in both non-diabetic and diabetic individuals, and how this mechanism becomes impaired over time. The research focus of my own laboratory and many others is directed by three principal questions. Where does the body sense a falling glucose? How does the body detect a falling glucose? And why does this mechanism fail in Type 1 diabetes? Hypoglycaemia is sensed by specialized neurons found in the brain and periphery, and of these the ventromedial hypothalamus appears to play a major role. Neurons that react to fluctuations in glucose use mechanisms very similar to those that operate in pancreatic B- and A-cells, in particular in their use of glucokinase and the KATP channel as key steps through which the metabolic signal is translated into altered neuronal firing rates. During hypoglycaemia, glucose-inhibited (GI) neurons may be regulated by the activity of AMP-activated protein kinase. This sensing mechanism is disturbed by recurrent hypoglycaemia, such that counter-regulatory defence responses are triggered at a lower glucose level. Why this should occur is not yet known, but it may involve increased metabolism or fuel delivery to glucose-sensing neurons or alterations in the mechanisms that regulate the stress response. [source] Role of orexin in the regulation of glucose homeostasisACTA PHYSIOLOGICA, Issue 3 2010H. Tsuneki Abstract Orexin-A (hypocretin-1) and orexin-B (hypocretin-2) are hypothalamic neuropeptides that play key roles in the regulation of wakefulness, feeding, reward, autonomic functions and energy homeostasis. To control these functions indispensable for survival, orexin-expressing neurones integrate peripheral metabolic signals, interact with many types of neurones in the brain and modulate their activities via the activation of orexin-1 receptor or orexin-2 receptor. In addition, a new functional role of orexin is emerging in the regulation of insulin and leptin sensitivities responsible for whole-body glucose metabolism. Recent evidence indicates that orexin efficiently protects against the development of peripheral insulin resistance induced by ageing or high-fat feeding in mice. In particular, the orexin receptor-2 signalling appears to confer resistance to diet-induced obesity and insulin insensitivity by improving leptin sensitivity. In fact, the expression of orexin gene is known to be down-regulated by hyperglycaemia in the rodent model of diabetes, such as ob/ob and db/db mice. Moreover, the levels of orexin receptor-2 mRNA have been shown to decline in the brain of mice along with ageing. These suggest that hyperglycaemia due to insulin insensitivity during ageing or by habitual consumption of a high-fat diet leads to the reduction in orexin expression in the hypothalamus, thereby further exacerbating peripheral insulin resistance. Therefore, orexin receptor controlling hypothalamic insulin/leptin actions may be a new target for possible future treatment of hyperglycaemia in patients with type 2 diabetes. [source] Structure and signaling in polyps of a colonial hydroidINVERTEBRATE BIOLOGY, Issue 1 2004Neil W. Blackstone Abstract. After feeding, polyps of colonial hydroids contract regularly, dispersing food throughout the colony via the gastrovascular fluid. Such contractions may trigger signaling pathways that allow colonies to grow in an adaptive manner, i.e., to initiate development of more polyps in food-rich areas and to suppress polyp development in food-poor areas. In this context, we investigated the structure and potential signaling of the junction between polyps and stolons in colonies of the hydroid Podocoryna carnea. Using transmission electron microscopy, we found that the density of mitochondrion-rich epitheliomuscular cells was low in polyp and stolon tissues except at or near the polyp-stolon junction, where many of these mitochondrion-rich cells occur in ectodermal tissue. In vivo fluorescence microscopy suggests that these mitochondria are a principal source of the metabolic signals of the colony. Both native fluorescence of NAD(P)H and fluorescence from peroxides (visualized with H2DCFDA) co-localize to this region of the polyp. Rhodamine 123 fluorescence suggests that both these metabolic signals emanate from mitochondria. To test whether such metabolic signals may be involved in colony pattern formation, inbred lines of P. carnea were used. Colonies of a runner-like inbred line grow with widely spaced polyps and long stolonal connections, much like wild-type colonies in a food-poor environment. Colonies of a sheet-like inbred line grow with closely spaced polyps and short stolonal connections, similar to wild-type colonies in a food-rich environment. Polyp-stolon junctions in runner-like and sheet-like colonies were imaged for the fluorescence of H2DCFDA. Densitometric analysis of this signal indicates that the mitochondria in epitheliomuscular cells of runner-like polyps emit greater amounts of peroxides. Because peroxides and other reactive oxygen species are frequently intermediaries in metabolic signaling pathways, we suspect that such signaling may indeed occur at polyp-stolon junctions, affecting colony pattern formation in these inbred lines and possibly in hydroid colonies in general. [source] Brain regulation of food intake and appetite: molecules and networksJOURNAL OF INTERNAL MEDICINE, Issue 4 2005C. BROBERGER Abstract. In the clinic, obesity and anorexia constitute prevalent problems whose manifestations are encountered in virtually every field of medicine. However, as the command centre for regulating food intake and energy metabolism is located in the brain, the basic neuroscientist sees in the same disorders malfunctions of a model network for how integration of diverse sensory inputs leads to a coordinated behavioural, endocrine and autonomic response. The two approaches are not mutually exclusive; rather, much can be gained by combining both perspectives to understand the pathophysiology of over- and underweight. The present review summarizes recent advances in this field including the characterization of peripheral metabolic signals to the brain such as leptin, insulin, peptide YY, ghrelin and lipid mediators as well as the vagus nerve; signalling of the metabolic sensors in the brainstem and hypothalamus via, e.g. neuropeptide Y and melanocortin peptides; integration and coordination of brain-mediated responses to nutritional challenges; the organization of food intake in simple model organisms; the mechanisms underlying food reward and processing of the sensory and metabolic properties of food in the cerebral cortex; and the development of the central metabolic system, as well as its pathological regulation in cancer and infections. Finally, recent findings on the genetics of human obesity are summarized, as well as the potential for novel treatments of body weight disorders. [source] Evidence for Increased Neuropeptide Y Synthesis in Mediobasal Hypothalamus in Relation to Parental Hyperphagia and Gonadal Activation in Breeding Ring DovesJOURNAL OF NEUROENDOCRINOLOGY, Issue 3 2007S. Ramakrishnan Like lactating mammals, male and female ring dove parents increase their food consumption to meet the energetic challenges of provisioning their young. To clarify the neurochemical mechanisms involved, the present study investigated the relationship between parental hyperphagia and changes in activity of the potent orexigen neuropeptide Y (NPY) in the hypothalamus of breeding doves. Changes in NPY-immunoreactive (NPY-ir) cell numbers in the tuberal hypothalamus of male and female doves were examined by immunocytochemistry at six stages of the breeding cycle. Parallel NPY mRNA measurements were recorded in mediobasal hypothalamus (which includes the tuberal hypothalamus) by semiquantitative reverse transcription-polymerase chain reaction using 18S rRNA as the internal standard. NPY mRNA changes were also measured in the mediobasal hypothalamus of nonbreeding doves following intracranial administration of prolactin, an orexigenic hormone that is elevated in the plasma of parent doves, and in response to food deprivation, which mimics the negative energy state that develops in parents as they provision their growing young. NPY-ir cell numbers in the tuberal hypothalamus and NPY mRNA levels in the mediobasal hypothalamus were significantly higher in breeding males and females during the period of parental hyperphagia after hatching than during the late incubation period when food intake remains unchanged. In nonbreeding doves, food deprivation and prolactin treatment increased NPY mRNA in this region by two- to three-fold, which suggests that NPY expression is sensitive to hormonal and metabolic signals associated with parenting. We conclude that NPY synthesis is increased in the mediobasal hypothalamus during the posthatching period, which presumably supports increased NPY release and resulting parental hyperphagia. NPY-ir and mRNA were also high in the mediobasal hypothalamus prior to egg laying when food intake remained unchanged. Several lines of evidence suggest that this elevation in NPY supports the increased gonadal activity that accompanies intense courtship and nest building interactions in breeding doves. [source] Rapid Vasodilation in Isolated Skeletal Muscle Arterioles: Impact of Branch OrderMICROCIRCULATION, Issue 2 2010BRUNO T. ROSEGUINI Microcirculation (2010) 17, 1,11. doi: 10.1111/j.1549-8719.2009.00005.x Abstract We tested the hypothesis that segmental differences in the responsiveness and time course of vasodilation to metabolic signals putatively involved in rapid onset vasodilation (ROV) at the start of exercise exist within the skeletal muscle vasculature. Cannulated first-order (1As) and third-order arterioles (3As) of the rat gastrocnemius (G) muscle were exposed to cumulative doses of KCl, acetylcholine (Ach), or adenosine (Ado). In addition, time course and magnitude of vasodilation to localized application of these agonists were determined. 1As and 3As dilated similarly to incremental doses of the agonists. Continuous monitoring of internal diameter revealed a fast and transient dilatory response to microinjections of the agonists, with an average time delay (TD) before the onset of vasodilation of 2.8 ± 0.2 seconds (1As: 3.0 ± 0.3 seconds and 3As: 2.6 ± 0.3 seconds) and time-to-peak (TP) of 8.2 ± 0.7 seconds (1As: 10.3 ± 1 seconds and 3As:5.7 ± 0.5 seconds). No significant differences were detected for all parameters between 1As and 3As for KCl or Ado application, while 1As had a significantly longer TP and greater peak dilation than 3As to Ach. These findings demonstrate that 1As and 3As from the rat G muscle appear to have similar responsiveness to vasoactive agonists. Furthermore, the average TD before vasodilation supports a role for metabolic signals as contributors to the ROV. [source] Crosstalk between Auxin, Cytokinins, and Sugars in the Plant Cell CyclePLANT BIOLOGY, Issue 3 2006K. Hartig Abstract: Plant meristems are utilization sinks, in which cell division activity governs sink strength. However, the molecular mechanisms by which cell division activity and sink strength are adjusted to a plant's developmental program in its environmental setting are not well understood. Mitogenic hormonal as well as metabolic signals drive and modulate the cell cycle, but a coherent idea of how this is accomplished, is still missing. Auxin and cytokinins are known as endogenous mitogens whose concentrations and timing, however, can be externally affected. Although the sites and mechanisms of signal interaction in cell cycle control have not yet been unravelled, crosstalk of sugar and phytohormone signals could be localized to several biochemical levels. At the expression level of cell cycle control genes, like cyclins, Cdks, and others, synergistic but also antagonistic interactions could be demonstrated. Another level of crosstalk is that of signal generation or modulation. Cytokinins affect the activity of extracellular invertases and hexose-uptake carriers and thus impinge on an intracellular sugar signal. With tobacco BY-2 cells, a coordinated control of cell cycle activity at both regulatory levels could be shown. Comparison of the results obtained with the root cell-representing BY-2 cells with literature data from shoot tissues or green cell cultures of Arabidopsis and Chenopodium suggests opposed and tissue-specific regulatory patterns of mitogenic signals and signal crosstalk in root and shoot meristems. [source] Ghrelin: more than a natural GH secretagogue and/or an orexigenic factorCLINICAL ENDOCRINOLOGY, Issue 1 2005E. Ghigo Summary Ghrelin, an acylated peptide produced predominantly by the stomach, has been discovered to be a natural ligand of the growth hormone secretagogue receptor type 1a (GHS-R1a). Ghrelin has recently attracted considerable interest as a new orexigenic factor. However, ghrelin exerts several other neuroendocrine, metabolic and also nonendocrine actions that are explained by the widespread distribution of ghrelin and GHS-R expression. The likely existence of GHS-R subtypes and evidence that the neuroendocrine actions, but not all the other actions, of ghrelin depend on its acylation in serine-3 revealed a system whose complexity had not been completely explored by studying synthetic GHS. Ghrelin secretion is mainly regulated by metabolic signals and, in turn, the modulatory action of ghrelin on the control of food intake and energy metabolism seems to be among its most important biological actions. However, according to a recent study, ghrelin-null mice are neither anorectics nor dwarfs and this evidence clearly depicts a remarkable difference from leptin null mice. Nevertheless, the original and fascinating story of ghrelin, as well as its potential pathophysiological implications in endocrinology and internal medicine, is not definitively cancelled by these data as GHS-R1a null aged mice show significant alterations in body composition and growth, in glucose metabolism, cardiac function and contextual memory. Besides potential clinical implications for natural or synthetic ghrelin analogues acting as agonists or antagonists, there are several open questions awaiting an answer. How many ghrelin receptor subtypes exist? Is ghrelin ,the' or just ,a' GHS-R ligand? That is, are there other natural GHS-R ligands? Is there a functional balance between acylated and unacylated ghrelin forms, potentially with different actions? Within the next few years suitable answers to these questions will probably be found, making it possible to gain a better knowledge of ghrelin's potential clinical perspectives. [source] | |||||||||||||