Submitted on May 1, 2009
Revised on May 22, 2009
Accepted on May 26, 2009
Dynamics of 
-Cell Turnover; Evidence for -Cell Turnover and Regeneration from Sources of -Cells other than -Cell Replication in the HIP rat
Erica Manesso1, Gianna Maria Toffolo1, Yoshifumi Saisho2, Alexandra Elizabeth Butler, Aleksey V Matveyenko3, Claudio Cobelli1, and Peter C. Butler3*
1 University of Padova
2 UCLA
3 David Geffen School of Medicine at UCLA
* To whom correspondence should be addressed. E-mail: pbutler{at}mednet.ucla.edu.
Type 2 diabetes is characterized by hyperglycemia, a deficit in 
-cells, increased -cell apoptosis, and islet amyloid derived from islet amyloid polypeptide (IAPP). These characteristics are recapitulated in the human IAPP transgenic (HIP) rat. We developed a mathematical model to quantify -cell turnover and applied it to non diabetic wild type (WT) versus HIP rats from age 2 days to 10 months to establish (1) if -cell formation is exclusively derived from -cell replication, or if other sources of -cells (OSB) are present, (2) to what extent, if any, there is attempted -cell regeneration in the HIP rat, and if this is through -cell replication or OSB. We conclude that formation and maintenance of adult -cells largely (~80%) depends on formation of -cells independent from -cell duplication. Moreover, this source adaptively increases in the HIP rat implying attempted -cell regeneration that substantially slows loss of -cell mass.
