Wiener Klinische Wochenschrift

, Volume 116, Issue 7–8, pp 217–229 | Cite as

Zukünftige Angriffspunkte für die Therapie des Typ-2-Diabetes

Übersicht

Zusammenfassung

Die Prävention und Behandlung des Typ-2-Diabetes mellitus (T2DM) und des metabolischen Syndroms stellen eine große klinische Herausforderung dar, da wirksame therapeutische Strategien wie fettarme Diät und körperliche Bewegung derzeit nur unzureichend umgesetzt werden. Aufgrund des zunehmenden Wissens über die Pathogenese des T2DM werden neue Therapieansätze geprüft. Angriffspunkte solcher Therapieformen sind (i) die Hemmung der Glukose-produktion der Leber, (ii) die Stimulation der Glukoseabhängigen Insulinsekretion, (iii) die Verbesserung der Insulin-Signaltransduktion und (iv) die Reduktion der Fettgewebsmasse. Agonisten des Glukagon-like-peptide (GLP-1) und Antagonisten der Dipeptidylpeptidase-IV, die GLP-1 abbauen, stimulieren die Glukose-abhängige Insulinsekretion, verbessern so die Hyperglykämie deutlich und sind bereits in klinischer Prüfung. Beim Menschen reduzieren Glukagon-Antagonisten sowie ein Amylin-Analog die Glukagon-abhängige Glukoseproduktion. Die Blutzucker-senkende Wirkung vorhandener Modulatoren der Lipidoxidation ist nicht ausgeprägt und könnte durch Nebenwirkungen limitiert sein. Neben bereits zugelassenen Thiazolidendion-Präparaten werden weitere Agonisten des peroxisome proliferator activator receptors γ (PPARγ) sowie kombinierte PPARα/γ-Agonisten untersucht. Die direkte Modulation der Insulin-Signaltransduktion ist derzeit noch auf experimentelle Untersuchungen beschränkt.

Schlüsselwörter

Diabetes mellitus Glukoseproduktion Insulinsensitizer Insulinsekretion Lipidoxidation 

Future targets in the treatment of type 2 diabetes

Summary

Prevention and treatment of type 2 diabetes mellitus (T2DM) and the metabolic syndrome represent a major clinical challenge, because effective strategies such as fat restriction and exercise are difficult to implement into diabetes treatment. Based on the increasing knowledge on the pathogenesis of T2DM, new therapeutic approaches are currently under investigation. Potential targets of new therapeutic approaches include: (i) Inhibition of hepatic glucose production, (ii) stimulation of glucose-dependent insulin secretion, (iii) enhancement of insulin signal transduction, and (iv) reduction of body fat mass. Agonists of glucagon-like-peptide 1 (GLP-1) and antagonists of dipeptidylpeptidase IV, which inactivates GLP-1, stimulate glucose-dependent insulin secretion, improve hyperglycemia and are already tested in clinical trials. In humans, glucagon antagonists and an amylin analogue reduce glucagon-dependent glucose production. The glucose-lowering effect of current modulators of lipid oxidation is not pronounced and their use could be limited by side effects. In addition to clinically approved thiazolidendiones, new agonists of the peroxisome proliferator activator receptor γ (PPARγ) as well as combined PPAR α/γ agonists are developed at present. The direct modulation of insulin signal transduction is still limited to experimental studies.

Key words

Diabetes mellitus glucose production insulin sensitizer insulin secretion lipid oxidation 

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© Springer 2004

Authors and Affiliations

  1. 1.Klinische Abteilung für Endokrinologie und StoffwechselUniversitätslinik für Innere Medizin III, Medizinische Universität WienWienÖsterreich
  2. 2.Medizinische AbteilungHanusch KrankenhausWienÖsterreich

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