Exp Clin Endocrinol Diabetes 2006; 114 - OR7_40
DOI: 10.1055/s-2006-932878

Adipocyte-derived factors activate Wnt-signaling in beta-cells and induce beta-cell proliferation

S Schinner 1, C Papewalis 1, M Schott 1, F Kocaoglu 1, SR Bornstein 2, WA Scherbaum 1
  • 1University Hospital Duesseldorf, Department of Endocrinology, Diabetes and Rheumatology, Duesseldorf, Germany
  • 2Carl Gustav Carus University, University Clinic III, Dresden, Germany

Introduction: The metabolic syndrome is characterised by obesity, insulin resistance, hyperinsulinemia and beta-cell hyperplasia. Recently, it has been shown that adipocytes secrete Wnt signaling molecules, and the Wnt-signaling pathway has been identified as a regulator of adipocyte function and beta-cell function. However, it has not been investigated, whether adipocytes act on target cells through the Wnt-signaling pathway.

Objectives: We investigated the effect of adipocyte secretory products on Wnt-signaling in beta-cells.

Results: We analysed histological pancreas sections of NZO (New Zealand Obese) mice, representing a model for the human metabolic syndrome, and found beta-cell hyperplasia as well as a massive increase in ectopic intrapancreatic adipocyte depots as compared to wildtype mice. In addition, adipocytes were found to be in contact with pancreatic islets, suggesting an adipocyte-islet interaction. To assess the effect of adipocyte-derived factors on Wnt-signaling in beta-cells, we transientently transfected Ins-1 cells with a canonical Wnt reporter-gene (TOPFLASH) and treated these cells with human fat-cell conditioned-medium (FCCM). We found a 2.5-fold increase of Wnt-mediated trancription in Ins-1 cells after stimulation with FCCM for 24 hours. To further address the physiological relevance of this finding we investigated the effect of Wnts and FCCM on beta-cell proliferation as Wnts are known cell cycle regulators. As assessed by (3H)-thymidine incorporation we found Wnt3a conditioned-medium to lead to a twofold increase in beta-cell proliferation and this effect could be mimicked by fat-cell conditioned-medium. The proliferative effect of FCCM could be inhibited by sFRP-1, an extracellular inhibitor of Wnt-signaling.

Conclusion: These data show a functional interaction between adipocytes and pancreatic beta-cell through the Wnt-signaling pathway, resulting in induction of beta-cell proliferation. These results might represent a novel mechanism linking obesity to beta-cell hyperplasia.