ISSN:
1600-0625
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Recently, we demonstrated a direct role for leptin in skin repair. However, pair-fed experiments with caloric restricted ob/ob mice clearly suggested that resolution of insulin resistance also represents a pivotal process that contributes to an accelerated healing. Immunohistochemistry revealed wound keratinocytes to be the insulin-sensitive skin compartment, as the cells strongly expressed the insulin receptor (InsR). We now focused to analyze the expression and activation of insulin-signaling components in wound keratinocytes of healthy, diabetic, and leptin-treated mice. First, we observed a downregulation of the InsR expression in normal wounds, which is precisely co-regulated by a downregulation and phosphorylation-dependent inactivation of its negative regulator, the InsR-associated protein tyrosine phosphatase-1B (PTP-1B). In line, a strong expression of InsR during late repair was associated with an increased presence of a dephosphorylated and thus active PTP-1B and the InsR substrate (IRS)-1- and -2-signaling molecules, suggesting that the InsR, its negative regulator PTP-1B, and both IRS were functionally connected during healing. Impaired healing conditions were characterized by a loss of InsR, IRS-1, and -2 expression but paralleled by increased amounts of phosphorylation-inactived PTP-1B. This finding suggested a regulatory mechanism to compensate for the loss of insulin-signaling components and to allow a more efficient signaling from the reduced amount of remaining InsR and IRS-1/-2 during impaired healing. Interestingly, systemic treatment of ob/ob mice with leptin resolved the dysregulated availability of the insulin-signaling components: InsR/IRS expression was upregulated, and the amount of dephosphorylated and thus active PTP-1B co-increased in wounds of treated animals. Finally, our findings could be confirmed by analysis of in vivo activation of protein kinase B as one possible readout for insulin signaling.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.0906-6705.2004.0212ag.x
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