31 Moibi, J. A. Gupta, D. Jetton, T. L. Peshavaria, M. Desai, R. Leahy, J. L. 2007 Diabetes 56 1 88-95 Jan 0012-1797 (Print) 17192469 Male Insulin-Secreting Cells/drug effects/physiology/secretion Insulin/secretion Homeodomain Proteins/*genetics Glucose/pharmacology Cell Nucleus/physiology Animals Rats, Sprague-Dawley Rats RNA/genetics/isolation & purification Pancreatectomy PPAR gamma/*physiology PPAR alpha/genetics Microscopy, Confocal Trans-Activators/*genetics Reverse Transcriptase Polymerase Chain Reaction Reference Values Sprague-Dawley Microscopy Confocal In the 60% pancreatectomy (Px) rat model of beta-cell adaptation, normoglycemia is maintained by an initial week of beta-cell hyperplasia that ceases and is followed by enhanced beta-cell function. It is unknown how this complex series of events is regulated. We studied isolated islets and pancreas sections from 14-day post-Px versus sham-operated rats and observed a doubling of beta-cell nuclear peroxisome proliferator-activated receptor (PPAR)-gamma protein, along with a 2-fold increase in nuclear pancreatic duodenal homeobox (Pdx)-1 protein and a 1.4-fold increase in beta-cell nuclear Nkx6.1 immunostaining. As PPAR-gamma activation is known to both lower proliferation and have prodifferentiation effects in many tissues, we studied PPAR-gamma actions in INS-1 cells. A 3-day incubation with the PPAR-gamma agonist troglitazone reduced proliferation and increased Pdx-1 and Nkx6.1 immunostaining, along with glucokinase and GLUT2. Also, a 75% knockdown of PPAR-gamma using RNA interference lowered the mRNA levels of Pdx-1, glucokinase, GLUT2, and proinsulin II by more than half. Our results show a dual effect of PPAR-gamma in INS-1 cells: to curtail proliferation and promote maturation, the latter via enhanced expression of Pdx-1 and Nkx6.1. Additional studies are needed to determine whether there is a regulatory role for PPAR-gamma signaling in the beta-cell adaptation following a 60% Px in rats. DK56818/DK/NIDDK NIH HHS/United StatesDK59851/DK/NIDDK NIH HHS/United StatesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tUnited States http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17192469