beta-arrestin-1 competitively inhibits insulin-induced ubiquitination and degradation of insulin receptor substrate 1.

beta-arrestin-1 is an adaptor protein that mediates agonist-dependent internalization and desensitization of G-protein-coupled receptors (GPCRs) and also participates in the process of heterologous desensitization between receptor tyrosine kinases and GPCR signaling. In the present study, we determined whether beta-arrestin-1 is involved in insulin-induced insulin receptor substrate 1 (IRS-1) degradation. Overexpression of wild-type (WT) beta-arrestin-1 attenuated insulin-induced degradation of IRS-1, leading to increased insulin signaling downstream of IRS-1. When endogenous beta-arrestin-1 was knocked down by transfection of beta-arrestin-1 small interfering RNA, insulin-induced IRS-1 degradation was enhanced. Insulin stimulated the association of IRS-1 and Mdm2, an E3 ubiquitin ligase, and this association was inhibited to overexpression of WT beta-arrestin-1, which led by decreased ubiquitin content of IRS-1, suggesting that both beta-arrestin-1 and IRS-1 competitively bind to Mdm2. In summary, we have found the following: (i) beta-arrestin-1 can alter insulin signaling by inhibiting insulin-induced proteasomal degradation of IRS-1; (ii) beta-arrestin-1 decreases the rate of ubiquitination of IRS-1 by competitively binding to endogenous Mdm2, an E3 ligase that can ubiquitinate IRS-1; (iii) dephosphorylation of S412 on beta-arrestin and the amino terminus of beta-arrestin-1 are required for this effect of beta-arrestin on IRS-1 degradation; and (iv) inhibition of beta-arrestin-1 leads to enhanced IRS-1 degradation and accentuated cellular insulin resistance.

Embodied Prayer: the practice of prayer as Christian theology

This dissertation attempts to retrieve the integration of prayer and theology in the life of the church. Prayer is a spiritual and bodily theological activity that forms Christian identity and virtuous character. The bodily dimension of Christian prayer plays an essential role in theological understanding and moral formation. However, the embodiment of prayer has been mostly neglected in modern academic theology. This study highlights the significance of the body at prayer in theological studies and spiritual formation.

Chapter 1 presents Karl Barth’s theology of prayer as a model of the integration of prayer, theology, and Christian life (lex orandi, lex credendi, lex agendi). However, Barth’s attempt to overcome the dichotomy between theory and practice in theology did not pay much attention to embodiment of prayer. Through ritual studies and phenomenology (Marcel Mauss, Maurice Merleau-Ponty, and Pierre Bourdieu), chapter 2 shows why the bodily dimension of the practice of prayer should be recovered in theology and ministry; then it explains how Christians in the early and medieval church actually prayed with the body, how their bodily actions were understood in their theological paradigms, and how their actions contributed to the formation of Christian character. Chapter 3 narrows the focus to the formation of the heart in the making of Christian character. The practice of prayer has been emphasized not only as an expression of the inner heart of pray-ers but also as a channel of grace that shapes their affections as enduring dispositions of the heart. Furthermore, historically the bodily practice of prayer gave theological authority to the devout Christians who were marginalized in academic theology or ecclesiastical hierarchy, and Chapter 4 presents the lex orandi of praying women who gained their theological knowledge, wisdom, and authority through their exemplary practices of prayer (Catherine of Siena, Mechthild of Magdeburg, Julian of Norwich, Margery Kempe, and Teresa of Avila). These historical examples reveal how Christian communities appreciated and celebrated the theological voices from the margins, which developed from theological embodiments in prayer.

This dissertation concludes that academic theology needs to heed these diverse theological voices, which are nurtured through everyday practice, as an integral part of theological studies. Therefore, it calls for a new paradigm for understanding the relationship between theory and practice in theological education. The integration between theory and bodily practice is necessary for both academic theology and spiritual formation. A more holistic understanding of Christian practices will not only enhance the training of scholars and clergy but also give the laity their own theological voices that will enrich academic theology.