Zusammenfassung
Insulin ist wichtig bei der Regulation metabolischer und nichtmetabolischer Zellen: Mangelnde Wirksamkeit der Signaltransduktion (Insulinresistenz) stellt z. B. nicht nur den zentralen Pathomechanismus bei Diabetes mellitus vom Typ 2 dar, sondern ist über die Induktion endothelialer Dysfunktion auch relevant für den Prozess der Atherosklerose. Nicht zuletzt wird die epidermale Homöostase von Insulin maßgeblich beeinflusst. In diesem Artikel beschreiben wir die Einflüsse von Insulin auf Proliferation und Differenzierung humaner Keratinozyten sowie die Bedeutung der durch proinflammatorische Zytokine induzierten Insulinresistenz für die gestörte epidermale Homöostase, welche die Psoriasis charakterisiert. Kinasen, welche Signale des Insulinrezeptors einerseits sowie proinflammatorischer Zytokinrezeptoren andererseits vermitteln, stellen potenzielle Zielstrukturen für innovative Therapeutika dar. Derartige „small molecules“ würden primär die „epidermale Dysfunktion“ korrigieren und somit immumodulatorische Strategien herkömmlicher Biologika komplementieren.
Abstract
Insulin is a central player in the regulation of metabolic as well as non-metabolic cells: inefficient signal transduction (insulin resistance) not only represents the cornerstone in the pathogenesis of type 2 diabetes mellitus, but also drives atherosclerosis through inducing endothelial dysfunction. Last but not least epidermal homeostasis depends on insulin. We summarize the effects of insulin on proliferation and differentiation of human keratinocytes as well as the relevance of cytokine-induced insulin resistance for alterations in epidermal homeostasis characteristic for psoriasis. Kinases involved in both insulin- as well as cytokine-receptor signaling represent potential targets for innovative therapeutics. Such small molecules would primarily normalize “epidermal dysfunction”, thus complementing the immunomodulatory strategies of today’s biologics.
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Boehncke, WH., Boehncke, S. & Buerger, C. Jenseits der Immunpathogenese. Hautarzt 63, 178–183 (2012). https://doi.org/10.1007/s00105-011-2227-5
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DOI: https://doi.org/10.1007/s00105-011-2227-5