PMID- 21903749
OWN - NLM
STAT- MEDLINE
DCOM- 20120112
LR  - 20211020
IS  - 1521-0103 (Electronic)
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 339
IP  - 3
DP  - 2011 Dec
TI  - Modeling diabetes disease progression and salsalate intervention in Goto-Kakizaki 
      rats.
PG  - 896-904
LID - 10.1124/jpet.111.185686 [doi]
AB  - Type 2 diabetes mellitus (T2DM) arises owing to insulin resistance and beta-cell 
      dysfunction. Chronic inflammation is widely identified as a cause of T2DM. The 
      Goto-Kakizaki (GK) rat is a spontaneous rodent model for T2DM with chronic 
      inflammation. The purpose of this study was to characterize diabetes progression 
      in GK rats and evaluate the potential role of the anti-inflammatory agent 
      salsalate. The GK rats were divided into control groups (n = 6) and salsalate 
      treatment groups (n = 6), which were fed a salsalate-containing diet from 5 to 21 
      weeks of age. Blood glucose and salicylate concentrations were measured once a 
      week. Glucose concentrations showed a biphasic increase in which the first phase 
      started at approximately 5 weeks, resulting in an increase by 15 to 25 mg/dl and 
      a second phase at 14 to 15 weeks with an upsurge of more than 100 mg/dl. A 
      mechanism-based model was proposed to describe the natural diabetes progression 
      and salsalate pharmacodynamics by using a population method in S-ADAPT. Two 
      transduction cascades were applied to mimic the two T2DM components: insulin 
      resistance and beta-cell dysfunction. Salsalate suppressed both disease factors by a 
      fraction of 0.622 on insulin resistance and 0.134 on beta-cell dysfunction. The 
      substantial alleviation of diabetes by salsalate supports the hypothesis that 
      chronic inflammation is a pathogenic factor of diabetes in GK rats. In addition, 
      body weight and food intake were measured and further modeled by a 
      mechanism-based growth model. Modeling results suggest that salsalate reduces 
      weight gain by enhancing metabolic rate and energy expenditure in both GK and 
      Wister-Kyoto rats.
FAU - Cao, Yanguang
AU  - Cao Y
AD  - Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical 
      Sciences, State University of New York, Buffalo, NY 14260, USA.
FAU - Dubois, Debra C
AU  - Dubois DC
FAU - Sun, Hao
AU  - Sun H
FAU - Almon, Richard R
AU  - Almon RR
FAU - Jusko, William J
AU  - Jusko WJ
LA  - eng
GR  - R01 GM057980/GM/NIGMS NIH HHS/United States
GR  - GM57980/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110908
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Blood Glucose)
RN  - 0 (Salicylates)
RN  - V9MO595C9I (salicylsalicylic acid)
RN  - WIQ1H85SYP (Sodium Salicylate)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents, Non-Steroidal/blood/pharmacokinetics/*therapeutic use
MH  - Blood Glucose/analysis
MH  - Body Weight
MH  - Diabetes Mellitus, Type 2/*drug therapy/metabolism/pathology/*physiopathology
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - Male
MH  - Models, Biological
MH  - Random Allocation
MH  - Rats
MH  - Rats, Inbred WKY
MH  - Salicylates/blood/pharmacokinetics/*therapeutic use
MH  - Sodium Salicylate/blood/pharmacokinetics
MH  - *Software
PMC - PMC3226370
EDAT- 2011/09/10 06:00
MHDA- 2012/01/13 06:00
PMCR- 2012/12/01
CRDT- 2011/09/10 06:00
PHST- 2011/09/10 06:00 [entrez]
PHST- 2011/09/10 06:00 [pubmed]
PHST- 2012/01/13 06:00 [medline]
PHST- 2012/12/01 00:00 [pmc-release]
AID - jpet.111.185686 [pii]
AID - 3730724 [pii]
AID - 10.1124/jpet.111.185686 [doi]
PST - ppublish
SO  - J Pharmacol Exp Ther. 2011 Dec;339(3):896-904. doi: 10.1124/jpet.111.185686. Epub 
      2011 Sep 8.