TY - JOUR
T1 - Dynamics of β-cell turnover
T2 - Evidence for β-cell turnover and regeneration from sources of β-cells other than β-cell replication in the HIP rat
AU - Manesso, Erica
AU - Toffolo, Gianna M.
AU - Saisho, Yoshifumi
AU - Butler, Alexandra E.
AU - Matveyenko, Aleksey V.
AU - Cobelli, Claudio
AU - Butler, Peter C.
PY - 2009/8
Y1 - 2009/8
N2 - Type 2 diabetes is characterized by hyperglycemia, a deficit in β-cells, increased β-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 β-cell turnover and applied it to nondiabetic wild type (WT) vs. HIP rats from age 2 days to 10 mo to establish 1) whether β-cell formation is derived exclusively from β-cell replication, or whether other sources of β-cells (OSB) are present, and 2) to what extent, if any, there is attempted β-cell regeneration in the HIP rat and if this is through β-cell replication or OSB. We conclude that formation and maintenance of adult β-cells depends largely (∼80%) on formation of β-cells independent from β-cell duplication. Moreover, this source adaptively increases in the HIP rat, implying attempted β-cell regeneration that substantially slows loss of β-cell mass.
AB - Type 2 diabetes is characterized by hyperglycemia, a deficit in β-cells, increased β-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 β-cell turnover and applied it to nondiabetic wild type (WT) vs. HIP rats from age 2 days to 10 mo to establish 1) whether β-cell formation is derived exclusively from β-cell replication, or whether other sources of β-cells (OSB) are present, and 2) to what extent, if any, there is attempted β-cell regeneration in the HIP rat and if this is through β-cell replication or OSB. We conclude that formation and maintenance of adult β-cells depends largely (∼80%) on formation of β-cells independent from β-cell duplication. Moreover, this source adaptively increases in the HIP rat, implying attempted β-cell regeneration that substantially slows loss of β-cell mass.
KW - Diabetes mellitus
KW - Human islet amyloid polypeptide
KW - Mathematical model
UR - http://www.scopus.com/inward/record.url?scp=68049107145&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=68049107145&partnerID=8YFLogxK
U2 - 10.1152/ajpendo.00284.2009
DO - 10.1152/ajpendo.00284.2009
M3 - Article
C2 - 19470833
AN - SCOPUS:68049107145
SN - 0193-1849
VL - 297
SP - E323-E330
JO - American Journal of Physiology - Endocrinology and Metabolism
JF - American Journal of Physiology - Endocrinology and Metabolism
IS - 2
ER -