• self-assembling glucagon-like peptide 1-mimetic peptide amphiphiles for enhanced activity and proliferation of insulin-secreting cells

    جزئیات بیشتر مقاله
    • تاریخ ارائه: 1392/01/01
    • تاریخ انتشار در تی پی بین: 1392/01/01
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     current treatment for type 1 diabetes mellitus requires daily insulin injections that fail to produce physiological glycemic control. islet cell transplantation has been proposed as a permanent cure but is limited by loss of β-cell viability and function. these limitations could potentially be overcome by relying on the activity of glucagon-like peptide 1 (glp-1), which acts on β-cells to promote insulin release, proliferation and survival. we have developed a peptide amphiphile (pa) molecule incorporating a peptide mimetic for glp-1. this glp-1-mimetic pa self-assembles into one-dimensional nanofibers that stabilize the active secondary structure of glp-1 and can be cross-linked by calcium ions to form a macroscopic gel capable of cell encapsulation and three-dimensional culture. the glp-1-mimetic pa nanofibers were found to stimulate insulin secretion from rat insulinoma (rinm5f) cells to a significantly greater extent than the mimetic peptide alone and to a level equivalent to that of the clinically used agonist exendin-4. the activity of the glp-1-mimetic pa is glucose-dependent, lipid-raft dependent and partially pka-dependent consistent with native glp-1. the glp-1-mimetic pa also completely abrogates inflammatory cytokine-induced cell death to the level of untreated controls. when used as a pa gel to encapsulate rinm5f cells, the glp-1-mimetic pa stimulates insulin secretion and proliferation in a cytokine-resistant manner that is significantly greater than a non-bioactive pa gel containing exendin-4. due to its self-assembling property and bioactivity, the glp-1-mimetic pa can be incorporated into previously developed islet cell transplantation protocols with the potential for significant enhancement of β-cell viability and function.

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