Dynamics of beta-cell turnover: evidence for beta-cell turnover and regeneration from sources of beta-cells other than beta-cell replication in the HIP rat.
Type 2 diabetes is characterized by hyperglycemia, a deficit in beta-cells, increased beta-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 beta-cell turnover and applied it to nondiabetic wild type (WT) vs. HIP rats from age 2 days to 10 mo to establish 1) whether beta-cell formation is derived exclusively from beta-cell replication, or whether other sources of beta-cells (OSB) are present, and 2) to what extent, if any, there is attempted beta-cell regeneration in the HIP rat and if this is through beta-cell replication or OSB. We conclude that formation and maintenance of adult beta-cells depends largely ( approximately 80%) on formation of beta-cells independent from beta-cell duplication. Moreover, this source adaptively increases in the HIP rat, implying attempted beta-cell regeneration that substantially slows loss of beta-cell mass.
Manesso
Erica
E
1Department of Information Engineering, University of Padua, Padua, Italy.
Toffolo
Gianna M
GM
Saisho
Yoshifumi
Y
Butler
Alexandra E
AE
Matveyenko
Aleksey V
AV
Cobelli
Claudio
C
Butler
Peter C
PC
D000682:Amyloid / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D001786:Blood Glucose / Q000032:analysis; D002454:Cell Differentiation; D049109:Cell Proliferation; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D050417:Insulin-Secreting Cells / Q000473:pathology / Q000502:physiology*; D058228:Islet Amyloid Polypeptide; D008954:Models, Biological; D010179:Pancreas / Q000473:pathology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D012038:Regeneration / Q000502:physiology*
D000682:Amyloid; D001786:Blood Glucose; D058228:Islet Amyloid Polypeptide