Pathophysiological Events (pathophysiological + event)

Distribution by Scientific Domains


Selected Abstracts


Molecular mechanisms of insulin resistance

DIABETIC MEDICINE, Issue 6 2005
S. Schinner
Abstract Currently, we observe an epidemic expansion of diabetes mellitus. In subjects with Type 2 diabetes the resistance of fat, muscle and liver to insulin is the central pathophysiological event in the development of this disease. Genetic and environmental factors play a major role in this process, although the precise pathogenesis of insulin resistance and Type 2 diabetes is still largely unknown. However, recent studies have contributed to a deeper understanding of the molecular mechanisms underlying this process. In this review we therefore summarize the current developments in understanding the pathophysiological process of insulin resistance and Type 2 diabetes. Among the many molecules involved in the intracellular processing of the signal provided by insulin, insulin receptor substrate (IRS)-2, the protein kinase B (PKB)-, isoform and the forkhead transcription factor Foxo1a (FKHR) are of particular interest in this context as recent data have provided strong evidence that dysfunction of these proteins results in insulin resistance in-vivo. Furthermore, we have now increasing evidence that the adipose tissue not only produces free fatty acids that contribute to insulin resistance, but also acts as a relevant endocrine organ producing mediators (adipokines) that can modulate insulin signalling. The identification of the molecular pathophysiological mechanisms of insulin resistance and Type 2 diabetes is essential for the development of novel and more effective therapies to better treat our patients with insulin resistance and Type 2 diabetes. [source]


Molecular mechanism of a cross-talk between oestrogen and growth factor signalling pathways

GENES TO CELLS, Issue 8 2000
Shigeaki Kato
Oestrogen (E2) plays significant roles in variety of biological events such as the development and maintenance of female reproductive organs, bone and lipid metabolisms. More recently, from study of knock-out mice deficient in oestrogen receptor (ER) , and ER, it turned out that normal spermatogenesis requires the E2 actions. Furthermore, this female steroid hormone is also well known to be deeply involved in many pathophysiological events such as osteoporosis and cancer development in female reproductive organs. It is particularly well known that most breast cancer is dependent on E2 in its development. Such E2 actions are thought to be mediated through two subtypes of ERs. Growth factors have been shown to synergize in this E2 signalling pathway, although the actual molecular mechanism largely remains unknown. Recently, we found that the MAP kinase activated by growth factors phosphorylates the Ser118 residue of the human ER, A/B domain and this phosphorylation potentiates the N-terminal transactivation function (AF-1) of human ER,, indicating the possible molecular mechanism of a novel cross-talk between E2 and growth factor signalling pathways. More recently, we have identified a coactivator associating with the hER, AF-1 in a MAPK-mediated phosphorylation-dependent manner. In this review, the molecular mechanism of this cross-talk is discussed in terms of the transactivation function of ERs, and their coactivators. [source]


The role of insulin as an antithrombotic humoral factor

BIOESSAYS, Issue 1 2004
Kushal Chakraborty
Insulin is well known for its essential role in carbohydrate metabolism: insulin deficiency results in the development of diabetes mellitus. It has been known for many years that people with diabetes mellitus are predisposed to develop thrombotic diseases including myocardial infarction. It was thought that the thrombus formation was the consequence of impaired carbohydrate metabolism. In recent years, it has become apparent that insulin is capable of ameliorating several pathophysiological events, leading to the inhibition and dissolution of the formed thrombus in the system. These insulin-induced events include inhibition of platelet aggregation by prompting the synthesis of NO in platelet and prostacyclin in endothelial cells. Furthermore, insulin upregulates prostacyclin receptors and downregulates ,2 adrenergic receptor in platelets, thereby amplifying the inhibition of platelet aggregation. Insulin also releases tissue plasminogen activator, a potent thrombolytic enzyme, from the platelet membrane which dissolves the formed thrombus leading to the resumption of normal blood circulation. In effect, insulin could be an essential tool in the control of thrombotic disorders. BioEssays 26:91,98, 2004. © 2003 Wiley Periodicals, Inc. [source]


The biomolecule ubiquinone exerts a variety of biological functions,

BIOFACTORS, Issue 1-4 2003
Hans Nohl
Abstract The chemistry of ubiquinone allows reversible addition of single electrons and protons. This unique property is used in nature for aerobic energy gain, for unilateral proton accumulation, for the generation of reactive oxygen species involved in physiological signaling and a variety of pathophysiological events. Since several years ubiquinone is also considered to play a major role in the control of lipid peroxidation, since this lipophilic biomolecule was recognized to recycle ,-tocopherol radicals back to the chain-breaking form, vitamin E. Ubiquinone is therefore a biomolecule which has increasingly focused the interest of many research groups due to its alternative pro- and antioxidant activity. We have intensively investigated the role of ubiquinone as prooxidant in mitochondria and will present experimental evidences on conditions required for this function, we will also show that lysosomal ubiquinone has a double function as proton translocator and radical source under certain metabolic conditions. Furthermore, we have addressed the antioxidant role of ubiquinone and found that the efficiency of this activity is widely dependent on the type of biomembrane where ubiquinone exerts its chain-breaking activity. [source]


Kinin B1 receptors: key G-protein-coupled receptors and their role in inflammatory and painful processes

BRITISH JOURNAL OF PHARMACOLOGY, Issue 7 2004
Joćo B Calixto
Kinins are a family of peptides implicated in several pathophysiological events. Most of their effects are likely mediated by the activation of two G-protein-coupled receptors: B1 and B2. Whereas B2 receptors are constitutive entities, B1 receptors behave as key inducible molecules that may be upregulated under some special circumstances. In this context, several recent reports have investigated the importance of B1 receptor activation in certain disease models. Furthermore, research on B1 receptors in the last years has been mainly focused in determining the mechanisms and pathways involved in the process of induction. This was essentially favoured by the advances obtained in molecular biology studies, as well as in the design of selective and stable peptide and nonpeptide kinin B1 receptor antagonists. Likewise, development of kinin B1 receptor knockout mice greatly helped to extend the evidence about the relevance of B1 receptors during pathological states. In the present review, we attempted to remark the main advances achieved in the last 5 years about the participation of kinin B1 receptors in painful and inflammatory disorders. We have also aimed to point out some groups of chronic diseases, such as diabetes, arthritis, cancer or neuropathic pain, in which the strategic development of nonpeptidic oral-available and selective B1 receptor antagonists could have a potential relevant therapeutic interest. British Journal of Pharmacology (2004) 143, 803,818. doi:10.1038/sj.bjp.0706012 [source]