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

Erica Manesso, Gianna M. Toffolo, Yoshifumi Saisho, Alexandra E. Butler, Aleksey V. Matveyenko, Claudio Cobelli, Peter C. Butler

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)E323-E330
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume297
Issue number2
DOIs
Publication statusPublished - 2009 Aug

Keywords

  • Diabetes mellitus
  • Human islet amyloid polypeptide
  • Mathematical model

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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