Dynamics of -cell turnover: evidence for -cell turnover and regeneration from sources of -cells other than -cell replication in the HIP rat

Manesso E, Toffolo GM, Saisho Y, Butler AE, Matveyenko AV, Cobelli C, Butler PC. Dynamics of -cell turnover: evidence for -cell turnover and regeneration from sources of -cells other than -cell replication in the HIP rat. Am J Physiol Endocrinol Metab 297: E323–E330, 2009. First published May 26, 2009; doi:10.1152/ajpendo.00284.2009.—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 nondiabetic wild type (WT) vs. HIP rats from age 2 days to 10 mo to establish 1) whether -cell formation is derived exclusively from -cell replication, or whether other sources of -cells (OSB) are present, and 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 depends largely ( 80%) 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.