PMID- 21396168
OWN - NLM
STAT- MEDLINE
DCOM- 20120308
LR  - 20111122
IS  - 1555-3892 (Electronic)
IS  - 0963-6897 (Linking)
VI  - 20
IP  - 9
DP  - 2011
TI  - Combination therapy with a dipeptidyl peptidase-4 inhibitor and a proton pump 
      inhibitor induces beta-cell neogenesis from adult human pancreatic duct cells 
      implanted in immunodeficient mice.
PG  - 1343-9
LID - 10.3727/096368910X557263 [doi]
AB  - Combination therapy with a dipeptidyl peptidase-4 inhibitor (DPP-4i) and a proton 
      pump inhibitor (PPI) raises endogenous levels of GLP-1 and gastrin, respectively, 
      and restores pancreatic beta-cell mass and normoglycemia in nonobese diabetic (NOD) 
      mice with autoimmune diabetes. The aim of this study was to determine whether a 
      DPP-4i and PPI combination could increase beta-cell mass in the adult human 
      pancreas. Pancreatic cells from adult human pancreas donors were implanted in 
      NOD-severe combined immunodeficient (NOD-scid) mice and the mice were treated 
      with a DPP-4i and a PPI for 16 weeks. Human grafts were examined for insulin 
      content and insulin-stained cells. Graft beta-cell function was assessed by 
      intravenous glucose tolerance tests (IVGTT) and by glucose control in human 
      cell-engrafted mice treated with streptozotocin (STZ) to delete mouse pancreatic 
      beta-cells. Plasma GLP-1 and gastrin levels were raised to two- to threefold in 
      DPP-4i- and PPI-treated mice. Insulin content and insulin-stained cells in human 
      pancreatic cell grafts were increased 9- to 13-fold in DPP-4i and PPI-treated 
      mice and insulin-stained cells were colocalized with pancreatic exocrine duct 
      cells. Plasma human C-peptide responses to IVGTT were significantly higher and 
      STZ-induced hyperglycemia was more completely prevented in DPP-4i- and 
      PPI-treated mice with grafts than in vehicle-treated mice with grafts. In 
      conclusion, DPP-4i and PPI combination therapy raises endogenous levels of GLP-1 
      and gastrin and greatly expands the functional beta-cell mass in adult human 
      pancreatic cells implanted in immunodeficient mice, largely from pancreatic duct 
      cells. This suggests that a DPP-4i and PPI combination treatment may provide a 
      pharmacologic therapy to correct the beta-cell deficit in type 1 diabetes.
FAU - Suarez-Pinzon, Wilma L
AU  - Suarez-Pinzon WL
AD  - Department of Medicine, University of Alberta, Edmonton, AB, Canada.
FAU - Rabinovitch, Alex
AU  - Rabinovitch A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110308
PL  - United States
TA  - Cell Transplant
JT  - Cell transplantation
JID - 9208854
RN  - 0 (Dipeptidyl-Peptidase IV Inhibitors)
RN  - 0 (Proton Pump Inhibitors)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Cell Transplantation
MH  - Dipeptidyl-Peptidase IV Inhibitors/*pharmacology
MH  - Drug Therapy, Combination
MH  - Female
MH  - Humans
MH  - Insulin-Secreting Cells/*drug effects/pathology
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, SCID
MH  - Organogenesis/*drug effects
MH  - Pancreatic Ducts/*cytology/drug effects/*transplantation
MH  - Proton Pump Inhibitors/*pharmacology
EDAT- 2011/03/15 06:00
MHDA- 2012/03/09 06:00
CRDT- 2011/03/15 06:00
PHST- 2011/03/15 06:00 [entrez]
PHST- 2011/03/15 06:00 [pubmed]
PHST- 2012/03/09 06:00 [medline]
AID - ct0255suarezpinzonrabinovitch [pii]
AID - 10.3727/096368910X557263 [doi]
PST - ppublish
SO  - Cell Transplant. 2011;20(9):1343-9. doi: 10.3727/096368910X557263. Epub 2011 Mar 
      8.