Clinical conditions inducing beta cell proliferation in the adult human pancreas.

Aim: The study aims to identify organ donors with high levels of proliferating pancreatic beta cells, correlate

the presence of these cells to specific clinical conditions, and characterize the molecular pathways involved.

Objectives:
1) determine the level of beta cell proliferation in human organ donors.
2) determine the cellular specificity of the proliferative response.
3) correlate findings with clinical data and determine parameters that allow identification of organ donors with beta cell proliferation. 4) investigate if a regenerative pathway is operative in the pancreas that mimics the regenerative pathways in the liver.

There is a growing body of evidence that the development of type 2 DM is associated with a relative deficit in beta cell mass (Klöppel et al, 1985; Clark et al, 1988; Butler et al, 2003; Yoon et al, 2003; Ritzel et al, 2006). Stimulating beta cell growth should thus be investigated as a potential treatment for the disease. Until recently, it was assumed that the proliferative potential of adult human beta cells was limited as mitotic figures were only rarely observed. However, lineage tracing studies in rodents (Dor et al, 2004, 2006) showed that after partial pancreatectomy newly formed beta cells are predominantly derived from existing beta cells, indicating that the adult mouse beta cell retains a substantial capacity for growth.