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Mechanismen der Insulinresistenz

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Zusammenfassung

Unter Insulinresistenz wird i. allg. eine Abschwächung der insulininduzierten Glukoseaufnahme verstanden, die sich hauptsächlich in der Skelettmuskulatur als abgeschwächte Glykogensynthese auswirkt und die hinsichtlich der Plasma-Glukose-Homöostase teilweise kompensiert wird durch Hyperinsulinämie. Dabei sind andere Insulinwirkungen von dieser Resistenz nicht oder weniger betroffen und können über die Hyperinsulinämie zur Prävalenz von Hochdruck, Übergewicht, Dyslipoproteinämie und Typ-II-Diabetes beitragen.

Auf der Ebene der Insulinrezeptoren kann die Resistenz bedingt sein durch: muskelspezifische, präferentielle Expression der niedrig-affinen B-Isoform des Insulinrezeptors sowie — in sehr seltenen Fällen extremer Resistenz — durch verschiedene Mutationen im Gen des Insulinrezeptors oder durch Insulinrezeptorautoantikörper. Auf der Postrezeptorebene können Translokation und/oder Expression des insulinresponsiven Glukosetransporters GluT-4 regulatorisch vermindert werden über den Hexosamin-Stoffwechselweg bei Hyperglykämie plus Hyperinsulinämie, andererseits aber auch durch langanhaltenden Insulinmangel, wobei in diesem Falle die GluT-4 Hemmung/Verarmung teilweise cAMP-vermittelt erfolgt. Die insulinstimulierte Glykogensynthese in der Skelettmuskulatur kann auch gehemmt werden durch endogene Signalpeptide wie Amylin und „Calcitonin-gene-related-Peptide“ sowie durch Modulation der Endothelfunktion, der Durchblutung und der Kapillarrekrutierung in der Mikrozirkulation der Skelettmuskulatur.

Obwohl epidemiologische Daten für eine genetische Disposition zur Insulinresistenz sprechen, kann gegenwärtig unter den vielen an der Resistenz potentiell beteiligten Mechanismen keine plausible Präzisierung für eine spezifische Lokalisation dieser genetischen Disposition vorgeschlagen werden.

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