1,723,570 research outputs found

    UMNH:Mamm:6976

    No full text
    UMNH:Mamm:6976 Voucher specimen study ski

    Treatment with Go-6976, reverses hyperglycemia-induced insulin resistance in adipocytes.

    No full text
    <p><b>A.</b> Effect of Go-6976 on Glucose transport. Insulin sensitive (IS) Adipocytes were preincubated in 5 mM glucose while Glucose-induced insulin resistant, (GI-IR) were generated by preincubation in 25 mM glucose+0.6 nM insulin for 18 h. During serum and insulin deprivation for 2 h, adipocytes were received 0.3 mM Go-6976 or vehicle control during the last hour of incubation. Glucose (2DOG) uptake was determined in unstimulated (open bars, basal) or in insulin-stimulated (100 nM for 15 min; filled bars, Insulin) cells. <b>B.</b> Effect of Go-6976 on insulin-stimulated Akt phosphorylation. Adipocytes were treated as in A, following acute insulin stimulation, cell lysates were collected and both phospho-Akt and total AKT was measured. Quantification represents ratios of phosphoAKT/Total AKT protein expressed relative to ratios obtained in from control insulin sensitive (IS) adipocytes. <b>C.</b> The effects of rapamycin and Go-6976 on insulin-stimulated glucose transport. Adipocytes were treated as in A, except that only cells, which have been acutely stimulated with insulin, are shown. Go-6976 (0.3 mM) and rapamycin (100 nM) are added during the last hour of incubation. <b>D.</b> The effects of rapamycin and Go-6976 on insulin-stimulated Akt phosphorylation. Adipocytes were treated as in C, following acute insulin stimulation, cell lysates were collected and both phospho-Akt and total AKT was measured. Quantification represents ratios of phosphoAKT/Total AKT protein expressed relative to ratios obtained in from control insulin sensitive (IS) adipocytes. Statistical significance is indicated by *p<0.05, and ** = p<0.005 compared to controls with the same preincubation.</p

    Effect of Go-6976 on S6 Kinase activity.

    No full text
    <p>Adipocytes were preincubated for 18 h in 5 mM glucose (IS) or in 25 mM glucose+0.6 nM insulin (GI-IR). <b>A.</b> Acute insulin treatment (100 nM for 15 min) stimulated activating phosphorylation of S-6 kinase (8–10-fold) and of its substrate S-6 ribosomal protein (4–5-fold). Under basal conditions, GI-IR adipocytes exhibited enhanced S6K phosphorylation. For quantification purposes, unstimulated (<b>B</b>) and acute insulin-stimulated (<b>C</b>) samples were also analysed on separate gels with exposure to times adjusted to within linear ranges. Under these conditions it is evident that the acute insulin stimulated S6K activity was decreased in the GI-IR cells. This was further reduced by treatment with Go-6976 (1 mM for 1 h). Statistical significance is indicated by *p<0.05 vs. control without Go-6976, **p<0.001. n = 9.</p

    Go-6976 reverses hyperglycemia-induced insulin resistance independently of cPKC inhibition in adipocytes.

    Get PDF
    Chronic hyperglycemia induces insulin resistance by mechanisms that are incompletely understood. One model of hyperglycemia-induced insulin resistance involves chronic preincubation of adipocytes in the presence of high glucose and low insulin concentrations. We have previously shown that the mTOR complex 1 (mTORC1) plays a partial role in the development of insulin resistance in this model. Here, we demonstrate that treatment with Go-6976, a widely used "specific" inhibitor of cPKCs, alleviates hyperglycemia-induced insulin resistance. However, the effects of mTOR inhibitor, rapamycin and Go-6976 were not additive and only rapamycin restored impaired insulin-stimulated AKT activation. Although, PKCα, (but not -β) was abundantly expressed in these adipocytes, our studies indicate cPKCs do not play a major role in causing insulin-resistance in this model. There was no evidence of changes in the expression or phosphorylation of PKCα, and PKCα knock-down did not prevent the reduction of insulin-stimulated glucose transport. This was also consistent with lack of IRS-1 phosphorylation on Ser-24 in hyperglycemia-induced insulin-resistant adipocytes. Treatment with Go-6976 did inhibit a component of the mTORC1 pathway, as evidenced by decreased phosphorylation of S6 ribosomal protein. Raptor knock-down enhanced the effect of insulin on glucose transport in insulin resistant adipocytes. Go-6976 had the same effect in control cells, but was ineffective in cells with Raptor knock-down. Taken together these findings suggest that Go-6976 exerts its effect in alleviating hyperglycemia-induced insulin-resistance independently of cPKC inhibition and may target components of the mTORC1 signaling pathway

    The PKC Inhibitor Gö 6976 Blocks C-Type Natriuretic Peptide Activation of Guanylyl Cyclase B

    No full text
    Additional contributors: Jerid Robinson; Andrea Yoder; Darcy Flora; Deborah Dickey; Lincoln R. Potter (faculty mentor).This study characterizes the effects of the widely used protein kinase C inhibitor, Gö 6976, on NPR-B guanylyl cyclase activity as a means to identify its inhibitory mechanisms.Lou, Xiaoying. (2009). The PKC Inhibitor Gö 6976 Blocks C-Type Natriuretic Peptide Activation of Guanylyl Cyclase B. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/58238

    Going Beyond Counting First Authors in Author Co-citation Analysis

    Get PDF
    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

    Get PDF
    “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

    Get PDF
    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
    corecore