PMID- 25387052
OWN - NLM
STAT- MEDLINE
DCOM- 20160324
LR  - 20181113
IS  - 1944-9917 (Electronic)
IS  - 0888-8809 (Print)
IS  - 0888-8809 (Linking)
VI  - 29
IP  - 1
DP  - 2015 Jan
TI  - Increasing beta-cell mass requires additional stimulation for adaptation to 
      secretory demand.
PG  - 108-20
LID - 10.1210/me.2014-1265 [doi]
AB  - Type 2 diabetes mellitus (T2DM) is caused by relative insulin deficiency, 
      subsequent to both reduced beta-cell mass and insufficient insulin secretion, and 
      both augmenting beta-cell mass and beta-cell function are therapeutic strategies for 
      treating T2DM. However, the relative significance of increasing beta-cell mass vs 
      improving beta-cell stimulus secretion coupling remains unclear. We have developed a 
      mouse model that allows proliferation of beta-cells in adult mice without affecting 
      beta-cell function by inducible expression of the positive cell cycle regulator 
      cyclin A2 specifically in beta-cells. In these mice, when kept on a standard diet, 
      doubling of beta-cell mass does not result in altered glucose tolerance or 
      glucose-stimulated circulating insulin levels. Notably, a doubling of beta-cell mass 
      also does not confer improved glycemic control and ability of beta-cells to respond 
      to diabetogenic high-fat diet-induced glucose intolerance. However, in high-fat 
      diet-exposed mice, an increase in endogenous beta-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 beta-cell mass may not be sufficient to improve glycemic control in T2DM 
      without additional strategies to increase beta-cell stimulus secretion coupling.
FAU - Mondal, Prosenjit
AU  - Mondal P
AD  - Departments of Medicine (M.A.H.), Pediatrics (P.M., W.-J.S., Y.L., K.S.Y., 
      M.A.H.), and Biological Chemistry (M.A.H.), Johns Hopkins University, Baltimore, 
      Maryland 21287.
FAU - Song, Woo-Jin
AU  - Song WJ
FAU - Li, Yuanyuan
AU  - Li Y
FAU - Yang, Kil S
AU  - Yang KS
FAU - Hussain, Mehboob A
AU  - Hussain MA
LA  - eng
GR  - P30 DK079637/DK/NIDDK NIH HHS/United States
GR  - P60 DK079637/DK/NIDDK NIH HHS/United States
GR  - R01 DK081472/DK/NIDDK NIH HHS/United States
GR  - R01 DK101591/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Mol Endocrinol
JT  - Molecular endocrinology (Baltimore, Md.)
JID - 8801431
RN  - 0 (CCNA2 protein, mouse)
RN  - 0 (Cyclin A2)
RN  - 0 (Glp1r protein, mouse)
RN  - 0 (Glucagon-Like Peptide-1 Receptor)
RN  - 0 (Insulin)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Cell Count
MH  - Cell Proliferation
MH  - Cyclin A2/biosynthesis/genetics
MH  - Diabetes Mellitus, Type 2/*metabolism
MH  - Diet, High-Fat
MH  - Glucagon-Like Peptide-1 Receptor/metabolism
MH  - Glucose/*metabolism
MH  - Glucose Intolerance/metabolism
MH  - Glucose Tolerance Test
MH  - Insulin/*deficiency
MH  - Insulin-Secreting Cells/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Pancreas/cytology/metabolism
PMC - PMC4280528
EDAT- 2014/11/12 06:00
MHDA- 2016/03/25 06:00
PMCR- 2016/01/01
CRDT- 2014/11/12 06:00
PHST- 2014/11/12 06:00 [entrez]
PHST- 2014/11/12 06:00 [pubmed]
PHST- 2016/03/25 06:00 [medline]
PHST- 2016/01/01 00:00 [pmc-release]
AID - ME-14-1265 [pii]
AID - 10.1210/me.2014-1265 [doi]
PST - ppublish
SO  - Mol Endocrinol. 2015 Jan;29(1):108-20. doi: 10.1210/me.2014-1265.