PMID- 20190014
OWN - NLM
STAT- MEDLINE
DCOM- 20100611
LR  - 20220310
IS  - 1521-0103 (Electronic)
IS  - 0022-3565 (Linking)
VI  - 333
IP  - 3
DP  - 2010 Jun
TI  - A selective peroxisome proliferator-activated receptor alpha agonist, CP-900691, 
      improves plasma lipids, lipoproteins, and glycemic control in diabetic monkeys.
PG  - 844-53
LID - 10.1124/jpet.110.166736 [doi]
AB  - Peroxisome proliferator-activated receptors (PPARs) are involved in the 
      regulation of lipid and glucose metabolism. PPARgamma agonists improve insulin 
      sensitivity and hyperglycemia and are effective in treating type 2 diabetes 
      mellitus (T2DM), whereas PPARalpha agonists are used to treat dyslipidemia and 
      atherosclerosis. The goal here was to examine the efficacy of a selective 
      PPARalpha agonist 
      (S)-3-[3-(1-carboxy-1-methyl-ethoxy)-phenyl]-piperidine-1-carboxylic acid 
      4-trifluoromethyl-benzyl ester; CP-900691 on lipid, glycemic, and inflammation 
      indices in 14 cynomolgus monkeys with spontaneous T2DM maintained on daily 
      insulin therapy. Monkeys were dosed orally with either vehicle (n = 7) or 
      CP-900691 (3 mg/kg, n = 7) daily for 6 weeks. CP-900691 treatment increased 
      plasma high-density lipoprotein cholesterol (HDLC) (33 +/- 3 to 60 +/- 4 mg/dL, p 
      < 0.001) and apolipoprotein A1 (96 +/- 5 to 157 +/- 5 mg/dL, p < 0.001), reduced 
      plasma triglycerides (547 +/- 102 to 356 +/- 90 mg/dL, p < 0.01), and 
      apolipoprotein B (62 +/- 3 to 45 +/- 3 mg/dL, p < 0.01), improved the lipoprotein 
      index (HDL to non-HDLC ratio; 0.28 +/- 0.06 to 0.79 +/- 0.16, p < 0.001), 
      decreased body weight (p < 0.01) and C-reactive protein (CRP) (1700 +/- 382 to 
      304 +/- 102 ng/ml, p < 0.01), and increased adiponectin (1697 +/- 542 to 4242 +/- 
      1070 ng/ml, p < 0.001) compared with baseline. CP-900691 treatment reduced 
      exogenous insulin requirements by approximately 25% (p < 0.04) while lowering 
      plasma fructosamine from 2.87 +/- 0.09 to 2.22 +/- 0.17 mM (p < 0.05), indicative 
      of improved glycemic control. There were no changes in any of the aforementioned 
      parameters in the vehicle group. Because low HDLC and high triglycerides are well 
      established risk factors for cardiovascular disease, the marked improvements in 
      these parameters, and in glycemic control, body weight, and CRP, suggest that 
      CP-900691 may be of benefit in diabetic and obese or hyperlipidemic populations.
FAU - Wagner, Janice D
AU  - Wagner JD
AD  - Department of Pathology, Wake Forest University, Winston-Salem, North Carolina 
      27157, USA. jwagner@wfubmc.edu
FAU - Shadoan, Melanie K
AU  - Shadoan MK
FAU - Zhang, Li
AU  - Zhang L
FAU - Ward, Gina M
AU  - Ward GM
FAU - Royer, Lori J
AU  - Royer LJ
FAU - Kavanagh, Kylie
AU  - Kavanagh K
FAU - Francone, Omar L
AU  - Francone OL
FAU - Auerbach, Bruce J
AU  - Auerbach BJ
FAU - Harwood, H James Jr
AU  - Harwood HJ Jr
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100226
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (3-(3-(1-carboxy-1-methylethoxy)phenyl)piperidine-1-carboxylic acid 
      4-trifluoromethylbenzyl ester)
RN  - 0 (Adiponectin)
RN  - 0 (Blood Glucose)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Hypolipidemic Agents)
RN  - 0 (Lipids)
RN  - 0 (Lipoproteins)
RN  - 0 (PPAR alpha)
RN  - 0 (Piperidines)
RN  - 0 (Propionates)
RN  - 9007-41-4 (C-Reactive Protein)
SB  - IM
MH  - Adiponectin/blood
MH  - Animals
MH  - Area Under Curve
MH  - Blood Glucose/*metabolism
MH  - C-Reactive Protein/metabolism
MH  - Diabetes Mellitus, Type 2/*blood/*drug therapy/genetics
MH  - Dose-Response Relationship, Drug
MH  - Glucose Tolerance Test
MH  - Hypoglycemic Agents/*pharmacology
MH  - *Hypolipidemic Agents
MH  - Insulin Resistance
MH  - Lipids/*blood
MH  - Lipoproteins/*blood
MH  - Macaca fascicularis
MH  - PPAR alpha/*agonists
MH  - Piperidines/*pharmacology
MH  - Propionates/*pharmacology
MH  - Weight Loss/drug effects
EDAT- 2010/03/02 06:00
MHDA- 2010/06/12 06:00
CRDT- 2010/03/02 06:00
PHST- 2010/03/02 06:00 [entrez]
PHST- 2010/03/02 06:00 [pubmed]
PHST- 2010/06/12 06:00 [medline]
AID - jpet.110.166736 [pii]
AID - 10.1124/jpet.110.166736 [doi]
PST - ppublish
SO  - J Pharmacol Exp Ther. 2010 Jun;333(3):844-53. doi: 10.1124/jpet.110.166736. Epub 
      2010 Feb 26.