Skip to main content

01.12.2007 | Article | Ausgabe 12/2007

Diabetologia 12/2007

Renal carcinogenesis in models of diabetes in rats—metabolic changes are closely related to neoplastic development

Diabetologia > Ausgabe 12/2007
F. Dombrowski, L. Klotz, P. Bannasch, M. Evert
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1007/​s00125-007-0838-2) contains supplementary material, which is available to authorised users.



There is an increased risk of renal cell carcinoma (RCC) in human diabetes mellitus. We therefore examined the influence of hyperglycaemia and glucose-lowering treatment on nephrocarcinogenesis in rats.


Rats (n = 850), which were either spontaneously diabetic, streptozotocin-diabetic or normoglycaemic, were examined with special reference to Armanni–Ebstein lesions (AEL).


Irrespective of the cause of diabetes, diabetic but not normoglycaemic rats developed typical glycogenotic clear-cell AEL. AEL showed strong proliferative activity, which was nearly completely inhibited by EGF receptor blockade (Gefitinib treatment). Many findings suggested a stepwise development of RCCs from AEL. Whereas the number and size of RCCs gradually increased in all diabetic groups, beginning at 6 months after onset of diabetes, normoglycaemic controls did not developed RCC. After 28 months, up to 82% of diabetic animals had at least one RCC. In contrast to the proximal tubules, the distal tubular system, including glycogenotic AEL, had the same levels of enzyme activities as RCC (e.g. high glycogen phosphorylase and synthase activity, lack of glucose 6-phosphatase activity) and the same expression patterns of cytokeratin 7 and several growth factors, along with their receptors and signal transduction proteins (TGF-α, EGF receptor, IGF-I, IGF-I receptor, IGF-II receptor, insulin receptor substrate 1, v-raf-1 murine leukemia viral oncogene homologue 1 and mitogen activated protein kinase kinase 1). In addition, direct morphological transitions between distal tubules, AEL and RCCs were frequently observed. All these findings indicate a common origin and a precursor–product relationship of AEL and RCCs.


Nephrocarcinogenesis in diabetic rats results from sustained hyperglycaemia, resulting in an adaptive metabolic response, altered growth factor signalling and subsequent neoplastic transformation of the tubular epithelial cells.

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

e.Med Interdisziplinär

Für Ihren Erfolg in Klinik und Praxis - Die beste Hilfe in Ihrem Arbeitsalltag als Mediziner

Mit e.Med Interdisziplinär erhalten Sie Zugang zu allen CME-Fortbildungen und Fachzeitschriften auf

Alle e.Med Abos bis 30. April 2021 zum halben Preis!

Jetzt e.Med zum Sonderpreis bestellen!

Weitere Produktempfehlungen anzeigen
Nur für berechtigte Nutzer zugänglich
Über diesen Artikel

Weitere Artikel der Ausgabe 12/2007

Diabetologia 12/2007 Zur Ausgabe
  1. Sie können e.Med Innere Medizin 14 Tage kostenlos testen (keine Print-Zeitschrift enthalten). Der Test läuft automatisch und formlos aus. Es kann nur einmal getestet werden.

  2. Sie können e.Med Allgemeinmedizin 14 Tage kostenlos testen (keine Print-Zeitschrift enthalten). Der Test läuft automatisch und formlos aus. Es kann nur einmal getestet werden.

Neu im Fachgebiet Innere Medizin

Mail Icon II Newsletter

Bestellen Sie unseren kostenlosen Newsletter Update Innere Medizin und bleiben Sie gut informiert – ganz bequem per eMail.

© Springer Medizin