Document Detail


Increasing beta-cell mass requires additional stimulation for adaptation to secretory demand.
MedLine Citation:
PMID:  25387052     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 versus 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 (SD), 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 (HFD)-induced glucose intolerance. However, in HFD-exposed mice, an increase in endogenous β-cell mass confers increased potentiation of in vivo glucose-stimulated 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.
Authors:
Prosenjit Mondal; Woo-Jin Song; Yuanyuan Li; Kil S Yang; Mehboob A Hussain
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-11-11
Journal Detail:
Title:  Molecular endocrinology (Baltimore, Md.)     Volume:  -     ISSN:  1944-9917     ISO Abbreviation:  Mol. Endocrinol.     Publication Date:  2014 Nov 
Date Detail:
Created Date:  2014-11-11     Completed Date:  -     Revised Date:  2014-11-12    
Medline Journal Info:
Nlm Unique ID:  8801431     Medline TA:  Mol Endocrinol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  me20141265     Citation Subset:  -    
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