PMID- 22649556
OWN - NLM
STAT- MEDLINE
DCOM- 20121009
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 5
DP  - 2012
TI  - Topiramate-induced modulation of hepatic molecular mechanisms: an aspect for its 
      anti-insulin resistant effect.
PG  - e37757
LID - 10.1371/journal.pone.0037757 [doi]
LID - e37757
AB  - Topiramate is an antiepileptic drug known to ameliorate insulin resistance 
      besides reducing body weight. Albeit liver plays a fundamental role in regulation 
      of overall insulin resistance, yet the effect of topiramate on this organ is 
      controversial and is not fully investigated. The current work aimed to study the 
      potential hepatic molecular mechanistic cassette of the anti-insulin resistance 
      effect of topiramate. To this end, male Wistar rats were fed high fat/high 
      fructose diet (HFFD) for 10 weeks to induce obese, insulin resistant, 
      hyperglycemic animals, but with no overt diabetes. Two HFFD-groups received oral 
      topiramate, 40 or 100 mg/kg, for two weeks. Topiramate, on the hepatic molecular 
      level, has opposed the high fat/high fructose diet effect, where it significantly 
      increased adiponectin receptors, GLUT2, and tyrosine kinase activity, while 
      decreased insulin receptor isoforms. Besides, it improved the altered glucose 
      homeostasis and lipid profile, lowered the ALT level, caused subtle, yet 
      significant decrease in TNF-alpha, and boosted adiponectin in a dose dependent 
      manner. Moreover, topiramate decreased liver weight/, visceral fat weight/, and 
      epididymal fat weight/body weight ratios. The study proved that 
      insulin-resistance has an effect on hepatic molecular level and that the 
      topiramate-mediated insulin sensitivity is ensued partly by modulation of hepatic 
      insulin receptor isoforms, activation of tyrosine kinase, induction of GLUT2 and 
      elevation of adiponectin receptors, as well as their ligand, adiponectin, besides 
      its known improving effect on glucose tolerance and lipid homeostasis.
FAU - El-Abhar, Hanan S
AU  - El-Abhar HS
AD  - Department of Pharmacology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
FAU - Schaalan, Mona F
AU  - Schaalan MF
LA  - eng
PT  - Journal Article
DEP - 20120523
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Glucose Transporter Type 2)
RN  - 0 (Receptors, Adiponectin)
RN  - 0 (Slc2a2 protein, rat)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0H73WJJ391 (Topiramate)
RN  - 30237-26-4 (Fructose)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Diet, High-Fat
MH  - Fructose/administration & dosage/*analogs & derivatives/pharmacology
MH  - Glucose Tolerance Test
MH  - Glucose Transporter Type 2/metabolism
MH  - Insulin Resistance/*physiology
MH  - Intra-Abdominal Fat/drug effects
MH  - Liver/*drug effects/*physiology
MH  - Male
MH  - Organ Size/drug effects
MH  - Protein-Tyrosine Kinases/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, Adiponectin/metabolism
MH  - Topiramate
MH  - Tumor Necrosis Factor-alpha/metabolism
PMC - PMC3359316
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/06/01 06:00
MHDA- 2012/10/10 06:00
PMCR- 2012/05/23
CRDT- 2012/06/01 06:00
PHST- 2012/01/25 00:00 [received]
PHST- 2012/04/27 00:00 [accepted]
PHST- 2012/06/01 06:00 [entrez]
PHST- 2012/06/01 06:00 [pubmed]
PHST- 2012/10/10 06:00 [medline]
PHST- 2012/05/23 00:00 [pmc-release]
AID - PONE-D-12-02314 [pii]
AID - 10.1371/journal.pone.0037757 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(5):e37757. doi: 10.1371/journal.pone.0037757. Epub 2012 May 23.