1,721,032 research outputs found
Clinical view on the need to develop new anti-diabetic drugs
Type 2 diabetes mellitus is a chronic metabolic disorder that results from defects in both insulin secretion and insulin action. Type 2 diabetic individuals are also characterized by reduced Î2-cell mass likely due to increased cellular apoptosis. Traditional strategies to treat diabetes have been developed with the main purpose of reducing hyperglycemia, and include insulin sensitizers, α-glucosidase inhibitors, and Î2-cell secretagogues. However, available drugs do not fully correct the phenotypic abnormalities in diabetes (e.g., insulin resistance, insulin deficiency) and have limited tolerability. Additionally, several available therapies are associated with weight gain or enhanced risk of hypoglycemia. Thus, newer approaches are urgently required. Particular emphasis should be placed on developing pharmacological interventions that are dependent on physiological responses and adequately target underlying defects, such as obesity, insulin resistance, increased glucose output from the liver, secretory dysfunction, or apoptosis of the Î2-cell. Individual phenotypic and genetic characterization of the diabetic patients will allow to define more and more personalized and effective algorithms for the treatment of hyperglycemia. © 2005 Bentham Science Publishers Ltd
Insulin signalling in human adipose tissue
Adipose tissue is a critical regulator of energy balance and substrate metabolism, and synthesizes several different substances with endocrine or paracrine functions, which regulate the overall energetic homeostasis. An excessive amount of adipose tissue has been associated with the development of type 2 diabetes, premature atherosclerosis, and cardiovascular disease. It is believed that the adverse metabolic impact of visceral fat relies on a relative resistance to the action of insulin in this depot compared to other adipose tissue depots. However, information on insulin signalling reactions in human fat is limited. In this paper, we review the major insulin signalling pathways in adipocytes and their relevance for metabolic regulation, and discuss recent data indicating different signalling properties of visceral fat as compared to other fat depots, which may explain the metabolic and hormonal specificity of this fat tissue depot in humans. © 2006 Informa UK Ltd
Adipose tissue precursor cells
Stem cells are unique cells exhibiting self-renewing properties and the potential to differentiate into multiple specialized cell types. Totipotent or pluripotent stem cells are generally abundant in embryonic or fetal tissues, but the use of discarded embryos as sources of these cells raises challenging ethical problems. Adult stem cells can also differentiate into a wide variety of cell types. In particular, adult adipose tissue contains a pool of abundant and accessible m ultipotent stem cells, designated as adipose stem cells (ASCs), that are able to replicate as undifferentiated cells, to develop as mature adipocytes, and to differentiate into multiple other cell types along the mesenchymal lineage, including chondrocytes, myocytes and osteoblasts, and also into cells of neuroectodermal origin, including neurons and astrocytes. An impairment in the differentiation potential and biological function of ASCs may contribute to the development of obesity and related pathologies. In this review, we summarize different aspects of adipose derived stem cells with special reference to isolation, characterization and properties of these cell populations, their potential role in the pathogenesis of metabolic diseases, and prospective therapeutic applications. ©2010, Editrice Kurtis
Human adipose tissue stem cells: relevance in the pathophysiology of obesity and metabolic diseases and therapeutic applications.
Stem cells are unique cells exhibiting self-renewing properties and the potential
to differentiate into multiple specialised cell types. Totipotent or pluripotent stem
cells are generally abundant in embryonic or fetal tissues, but the use of
discarded embryos as sources of these cells raises challenging ethical
problems. Adult stem cells can also differentiate into a wide variety of cell
types. In particular, adult adipose tissue contains a pool of abundant and
accessible multipotent stem cells, designated as adipose-derived stem cells
(ASCs), that are able to replicate as undifferentiated cells, to develop as
mature adipocytes and to differentiate into multiple other cell types along the
mesenchymal lineage, including chondrocytes, myocytes and osteocytes, and
also into cells of endodermal and neuroectodermal origin, including beta-cells
and neurons, respectively. An impairment in the differentiation potential and
biological functions of ASCs may contribute to the development of obesity and
related comorbidities. In this review, we summarise different aspects of the
ASCs with special reference to the isolation and characterisation of these cell
populations, their relation to the biochemical features of the adipose tissue
depot of origin and to the metabolic characteristics of the donor subject and
discuss some prospective therapeutic applications
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Role of UBC9 in the regulation of the adipogenic program in 3T3-L1 adipocytes
The small ubiquitin-like modifier-conjugating enzyme UBC9, involved in protein modification through covalent attachment of small ubiquitin-like modifier and other less defined mechanisms, has emerged as a key regulator of cell proliferation and differentiation. To explore the role of UBC9 in adipocyte differentiation, the UBC9 protein levels were examined in differentiating 3T3-L1 cells. UBC9 mRNA and protein levels were increased 2.5-fold at d 2 and then gradually declined to basal levels at d 8 of differentiation. In addition, UBC9 was expressed predominantly in the nucleus of preadipocytes but shifted to cytoplasmic compartments after d 4, after induction of differentiation. UBC9 knockdown was then achieved in differentiating 3T3-L1 preadipocytes using a specific small interfering RNA. Oil-Red-O staining demonstrated accumulation of large triglyceride droplets in approximately 90% of control cells, whereas lipid droplets were smaller and evident in only 30% of cells treated with the UBC9-specific small interfering RNA. CCAAT/enhancer-binding protein (C/EBP)-δ, peroxisome proliferator-activated receptor-γ, and C/EBPα mRNA levels were increased severalfold 2-6 d after induction of differentiation in control cells, whereas the expression of these transcription factors was significantly lower in the presence of UBC9 gene silencing. Adenovirus-mediated overexpression of a catalytically inactive mutant UBC9 protein in 3T3-L1 cells resulted in no changes in expression of adipogenic transcription factors and conversion to mature adipocytes as compared with control. In conclusion, UBC9 appears to play an important role in adipogenesis. The temporal profile of UBC9 induction and its ability to affect C/EBPδ mRNA induction support a role for this protein during early adipogenesis
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