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Grundlagen




Definition: IGF-1 (Insulin-Like Growth Factor 1) ist ein 70-Ärmeliger Proteinpeptid, das vorwiegend in der Leber unter Einfluss von Wachstumshormon (GH) synthetisiert wird.


Aufbau: Besteht aus 70 Aminosäuren, zwei disulfidgebundenen Schleifen und einer C-Terminal-Region. Die Bindung an IGF-1-Rezeptoren (IGF-1R) löst die Phosphorylierung von Tyrosin-Residenzen in der intracellularen Domäne aus.


Bindungsproteine: 6 insulino-ähnliche Wachstumsfaktor-Binding-Proteine (IGFBP-1 bis 6). IGFBP-3 bindet etwa 75 % des Circulants und verlängert die Halbwertszeit, während IGFBP-2 und IGFBP-5 als Antagonisten wirken.









Physiologische Funktionen



System Hauptfunktion


Knochen Stimulation der Osteoblasten; Knochenmasseerhalt (z.B. bei Kindern, Jugendlichen).


Muskel Anabole Wirkung – Proteinsynthese, Muskelhypertrophie.


Herz/Kreislauf Cardio-protektion, Verbesserung der Myokardiale Kontraktilität, Regulation des Blutdrucks.


Neuroendokrine Neuroprotektive Effekte, Regulation von Lern- und Gedächtnisprozessen.


Metabolisch Modulation der Glukose- und Lipid-Hämodynamik, Sensibilisierung gegenüber Insulin.



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Klinische Relevanz



a) Wachstumsspektrum


Kinder/Adoleszenten: IGF-1-Mangel → Wachstumsverzögerung; Überschuss kann zu Gigantismus führen.


Erwachsene: Serum-IGF-1 spiegelt die GH-Secretion wider. Diagnostik bei Verdacht auf GH-Defizienz, Skelettdeformitäten oder metabolischen Störungen.



b) Metabolische Erkrankungen


Diabetes mellitus Type 2: Niedrige IGF-1-Konzentrationen korrelieren mit Insulinresistenz. Therapeutische Ansätze zielen auf Verbesserung der IGF-1-Signalgebung.


Adipositas: IGFBP-3 wird reduziert, IGFBP-5 erhöht – mögliche Marker für metabolisches Syndrom.



c) Herz-Kreislauf


Chronische Herzinsuffizienz: Niedrige IGF-1-Spiegel prognostisch negativ. Intravenöse IGF-1-Supplementation in Studien mit Verbesserung der Lungenfunktion, aber nicht eindeutig mortality-reduzierend.


Akuter Myokardinfarkt: IGF-1 schützt vor Nekrose; therapeutische Anwendung noch experimental.



d) Onkologie


IGF-1R-Signalierung kann Tumorprogression fördern. IGF-1R-Antikörper (Ex. ganitumab, figitumab) sind in klinischen Studien, allerdings mit begrenztem Erfolg und signifikanten Nebenwirkungen.








Messung & Interpretation



Parameter Referenzbereich (Kinder / Erwachsene) Hinweis


Serum-IGF-1 9–30 ng/ml (je nach Alter, Geschlecht) Altersabhängig; bestes Ergebnis bei Morgenabstrich.


IGFBP-3 1,5–4,0 g/L Reflektiert GH-Aktivität; kann mit IGF-1 vergleichen.


IGF-1-Rezeptor-Titer – In der Praxis selten verwendet.





Interpretation:


- Erhöhter IGF-1 bei normalem IGFBP-3 → mögliche GH-Überschuss (Gigantismus).

- Niedriger IGF-1 trotz hoher IGFBP-3 → GH-Defizienz oder endokrine Resistenz.




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Therapieansätze



Indikation Ansatz Evidenz


GH-Defizienz Recombinant GH (somatropin) Hochgradig evidenzbasiert, IGF-1 dient als Zielwert.


Adipositas/Metabolisches Syndrom Lebensstil + ggf. GH-Analogon Zwischenergebnisse; keine klare Empfehlung.


Herzinsuffizienz IGF-1-Supplement (IV) Pilotstudien, aber keine Routineempfehlung.


Onkologie IGF-1R-Antikörper Phase III-Studien negativ → Nicht empfohlen.



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Nebenwirkungen & Risiken




GH/IGF-1-Therapie: Ödeme, Gelenkschmerzen, Hyperglykämie, mögliche Tumorproliferation.


IGFBP-Modulation: Risiko der Dysregulation des IGF-1-Systems; bislang nicht therapeutisch genutzt.









Aktuelle Forschungsfelder



IGF-1 und neurodegenerative Erkrankungen – Neuroprotektive Wirkungen bei Alzheimer & Parkinson werden untersucht.


IGFBP-3 als Biomarker für kardiovaskuläre Risiken in der Prävention.


CRISPR-basierte Modulation von IGF-1-R im Muskel zur Behandlung von Muskeldystrophien.








Fazit



IGF-1 ist ein zentrales Mediator des Wachstums, Metabolismus und der Zellproliferation. Die Messung dient primär als Spiegel der GH-Aktivität, doch ihre Rolle in metabolischen, kardiovaskulären und onkologischen Kontexten gewinnt zunehmend an Bedeutung. Klinische Entscheidungen sollten auf einer sorgfältigen Analyse von IGF-1, IGFBP-3 und den klinischen Befunden basieren, wobei die Therapie immer im Rahmen der evidenzbasierten Leitlinien erfolgt.
Der insulinähnliche Wachstumsfaktor 1 (IGF-1) spielt eine zentrale Rolle im menschlichen Körper. Er ist ein Peptidhormon, das hauptsächlich in der Leber produziert wird und durch die Aktivität des Wachstumshormons (GH) reguliert wird. IGF-1 wirkt als Mediator für viele physiologische Prozesse wie Zellteilung, Differenzierung, Überleben und Stoffwechselregulation. Durch seine Wirkung kann er sowohl im Körperwachstum als auch bei der Reparatur von Geweben eine entscheidende Rolle spielen.



Definition
IGF-1 ist ein 70-Residuen-Peptid, das in seiner strukturellen Anordnung dem Insulin ähnlich ist. Es bindet an spezifische IGF-1-Rezeptoren auf Zelloberflächen und löst intrazelluläre Signalwege aus, die letztlich zur Aktivierung von Proteinen wie Akt, MAPK oder mTOR führen. Diese Signalwege fördern die Proliferation von Zellen, hemmen Apoptose und beeinflussen den Stoffwechsel von Kohlenhydraten, Fetten und Proteinen.



Herstellung und Regulation
Die Synthese von IGF-1 wird durch das Wachstumshormon stimuliert, welches im Hypophysenhinterlappen ausgeschüttet wird. Sobald GH die Leber erreicht, bindet es an dessen Rezeptor und initiiert die Transkription des IGF-1-Gens. Im Blutkreislauf wird IGF-1 jedoch nicht frei zirkulieren; stattdessen ist es in der Regel an IGF-Binding-Proteine (IGFBPs) gebunden, hauptsächlich IGFBP-3. Diese Bindung stabilisiert das Hormon und reguliert seine bioverfügbare Menge.



Normwerte
Die Normwerte für IGF-1 variieren je nach Alter, Geschlecht und Laborbedingungen. Generell liegen die Werte im Kindesalter bei etwa 100 bis 300 µg/L, während sie bei Erwachsenen typischerweise zwischen 70 und 200 µg/L liegen. Bei älteren Menschen sinken die Konzentrationen allmählich ab, was mit einem natürlichen Teil des Alterungsprozesses zusammenhängt.



Messverfahren
Zur Bestimmung von IGF-1 werden üblicherweise ELISA- oder RIA-Methoden eingesetzt. Das Blut wird in der Regel morgens entnommen, da es diurnal variation gibt. Die Messung liefert sowohl den Gesamtwert als auch die freies IGF-1, wenn spezielle Assays verwendet werden.



Pathologische Zustände
Ein zu hoher IGF-1-Spiegel kann auf Akromegalie hinweisen, eine Erkrankung, bei der die Hypophyse übermäßig GH produziert. Umgekehrt kann ein niedriger IGF-1-Wert in Verbindung mit Wachstumsstörungen oder Knochenerkrankungen stehen. In beiden Fällen ist eine weitere diagnostische Abklärung notwendig.



Therapeutischer Einsatz
In den letzten Jahren wurden synthetische Formen von IGF-1 entwickelt, um bei bestimmten Erkrankungen wie Muskeldystrophien oder nach Operationen die Regeneration zu fördern. Die Anwendung erfordert jedoch sorgfältige Dosierung und Überwachung, da Nebenwirkungen auftreten können.



Fazit
IGF-1 ist ein multifunktionales Hormon mit bedeutender Rolle im Wachstum, Stoffwechsel und Gewebeerneuerung. Seine Messung liefert wichtige diagnostische Informationen, insbesondere bei Erkrankungen des Hypophysensystems oder bei Wachstumsstörungen. Ein umfassendes Verständnis seiner Biochemie und physiologischen Wirkungsweise ist entscheidend für die korrekte Interpretation von Laborwerten und die Planung therapeutischer Interventionen.

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