Ätiopathogenese des Typ-1-Diabetes mellitus

Zusammenfassung

Der Diabetes mellitus Typ 1 ist eine durch Umweltfaktoren ausgelöste Autoimmunerkrankung, die genetisch empfängliche Personen trifft. Begünstigende Umweltfaktoren sind Nahrungsmittel, wie Kuhmilchprotein, virale Infekte und unterschiedliche Umweltgifte, wie Nitrosamine. Typ-1-Diabetes wird als zellvermittelte Autoimmunerkrankung mit progressiver Zerstörung der insulinproduzierenden Beta-Zellen verstanden. Dabei spielt die Aktivierung proapoptotischer Signalwege (programmierter Zelltod) durch inflammatorische Zytokine eine Schlüsselrolle beim Zelltod der β-Zellen. Den T-Lymphozyten vom so genannten Helfer-Typ (Th1) wird dabei eine zentrale Rolle zugeschrieben. Zytokine, die überwiegend von Th1-Zellen sezerniert werden, sind Interleukin-1 (IL-1)β, Interferon (IFN)-γ und Tumor-Nekrose-Faktor (TNF)α. Die Produktion dieser proinflammatorischen Zytokine wird einer Störung im fein abgestimmten Gleichgewicht zwischen Th1- und Th2-Helfer-T-Zellen zugeschrieben und führt zu einer selektiven Aktivierung von Beta-Zell-spezifischen, zytotoxischen Effektor-T-Zellen. Durch eine weitere Aufschlüsselung der Ätiopathogenese des Typ-1-Diabetes mellitus sollen neue Strategien in dessen Prävention und Heilung entwickelt werden.

Summary

Type 1 diabetes mellitus results from a progressive loss of pancreatic beta cell number. Environmental factors such as exposure to cow’s milk protein, viral infections and toxins such as nitrosamines are thought to play a pivotal role in the development of type 1 diabetes by influencing the penetrance of diabetes susceptibility genes. The local production of cytokines such as tumour necrosis factor-alpha (TNFα), interleukin-1 beta (Il-1β) and the synthesis of nitric oxide (NO) are known to induce programmed cell death of pancreatic beta cells. The molecular mechanisms and the cell’s machinery leading to and enhancing apoptosis/programmed cell death have been elucidated. The production of pro-inflammatory cytokines is thought to be a consequence of the disruption of the finely tuned immune balance of Th1-helper and Th2-helper T lymphocytes. This derangement of the immune system leads to the selective activation of beta-cell-cytotoxic effector T cells. It is hoped that the knowledge of the aetiopathogenesis of type 1 diabetes will help to further develop strategies to prevent and ultimately cure the disease.

Schlüsselwörter

Diabetes mellitus Typ 1 - Autoimmunerkrankung - Umweltfaktoren - Apoptose - Zytokine - Th1/Th2-Immunität

Keywords

Type 1 diabetes mellitus - autoimmune disease - environmental factors - apoptosis - cytokines - Th1-helper cells - Th2-helper cells

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