Dickkopf-3 is expressed in a subset of adult human pancreatic beta-cells

Objectives: The Dickkopf (Dkk) gene family of secretory modulators of canonical Wnt/beta-catenin signals is involved in the control of stem cell proliferation, homeostasis, and differentiation. Bioinformatic data on dkk-1/3 gene expression, indicating high expression levels in the human pancreas, led us to analyze these two proteins in adult human pancreatic tissue.

Methods: Paraffin embedded normal human adult pancreatic tissue sections were obtained from US Biomax Inc. Human islets were isolated according to the method of Ricordi et al., 1988.

Results: Dkk-1/3 mRNA levels and protein distribution was analyzed in isolated human islets vs. the exocrine/ductal pancreatic cells and in paraffin sections of adult human pancreata. Via real time PCR only lowest amounts of Dkk-1 mRNA were detectable in the endocrine fractions. Immunohistochemistry gave no signal for Dkk-1 in adult human pancreatic tissue. Interestingly, Dkk-3 mRNA and protein was clearly present in adult human pancreatic islets. Messenger RNA levels for Dkk-3 were significantly higher in isolated islets compared to the exocrine/ductal fraction. Costaining with an antibody against insulin identified the beta-cells of the pancreas as the Dkk-3-positive cells. Notably, only a subset of beta cells contained Dkk-3.

Conclusions: Our findings suggest a role of Dkk-3 in normal adult human islet physiology. To our knowledge, this is the first study describing a molecule with which the pool of prancreatic beta cells can further be subdivided. Future studies will show whether this subclassification of beta cells into those containing Dkk-3 and those being negative for this protein translates into functional differences such as the ability to regenerate.

Fig. 1 Costaining of Dkk-3 and insulin