Increasing β-cell mass requires additional stimulation for adaptation to secretory demand

Prosenjit Mondal, Woo Jin Song, Yuanyuan Li, Kil S. Yang, Mehboob A. Hussain

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Type 2 diabetes mellitus (T2DM) is caused by relative insulin deficiency, subsequent to both reduced β-cell mass and insufficient insulin secretion, and both augmenting β-cell mass and β-cell function are therapeutic strategies for treating T2DM. However, the relative significance of increasing β-cell mass vs improving β-cell stimulus secretion coupling remains unclear. We have developed a mouse model that allows proliferation of β-cells in adult mice without affecting β-cell function by inducible expression of the positive cell cycle regulator cyclin A2 specifically in β-cells. In these mice, when kept on a standard diet, doubling of β-cell mass does not result in altered glucose tolerance or glucose-stimulated circulating insulin levels. Notably, a doubling of β-cell mass also does not confer improved glycemic control and ability of β-cells to respond to diabetogenic high-fat diet-induced glucose intolerance. However, in high-fat diet-exposed mice, an increase in endogenous β-cell mass confers increased potentiation of in vivo glucosestimulated rise in circulating insulin in response to acute pharmacologic treatment with the incretin glucagon-like peptide-1 receptor agonist exendin-4. These observations indicate that increasing endogenous β-cell mass may not be sufficient to improve glycemic control in T2DM without additional strategies to increase β-cell stimulus secretion coupling.

Original languageEnglish (US)
Pages (from-to)108-120
Number of pages13
JournalMolecular Endocrinology
Issue number1
StatePublished - Jan 1 2015

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology


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