PMID- 23775767
OWN - NLM
STAT- MEDLINE
DCOM- 20131112
LR  - 20211021
IS  - 1939-327X (Electronic)
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 62
IP  - 9
DP  - 2013 Sep
TI  - Inverse agonist of nuclear receptor ERRgamma mediates antidiabetic effect through 
      inhibition of hepatic gluconeogenesis.
PG  - 3093-102
LID - 10.2337/db12-0946 [doi]
AB  - Type 2 diabetes mellitus (T2DM) is a progressive metabolic disorder with diverse 
      pathological manifestations and is often associated with abnormal regulation of 
      hepatic glucose production. Many nuclear receptors known to control the hepatic 
      gluconeogenic program are potential targets for the treatment of T2DM and its 
      complications. Nevertheless, the therapeutic potential of the estrogen-related 
      receptor gamma (ERRgamma) in T2DM remains unknown. In this study, we show that the 
      nuclear receptor ERRgamma is a major contributor to hyperglycemia under diabetic 
      conditions by controlling hepatic glucose production. Hepatic ERRgamma expression 
      induced by fasting and diabetic conditions resulted in elevated levels of 
      gluconeogenic gene expression and blood glucose in wild-type mice. Conversely, 
      ablation of hepatic ERRgamma gene expression reduced the expression of gluconeogenic 
      genes and normalized blood glucose levels in mouse models of T2DM: db/db and 
      diet-induced obesity (DIO) mice. In addition, a hyperinsulinemic-euglycemic clamp 
      study and long-term studies of the antidiabetic effects of GSK5182, the 
      ERRgamma-specific inverse agonist, in db/db and DIO mice demonstrated that GSK5182 
      normalizes hyperglycemia mainly through inhibition of hepatic glucose production. 
      Our findings suggest that the ability of GSK5182 to control hepatic glucose 
      production can be used as a novel therapeutic approach for the treatment of T2DM.
FAU - Kim, Don-Kyu
AU  - Kim DK
AD  - National Creative Research Initiatives Center for Nuclear Receptor Signals and 
      Hormone Research Center, School of Biological Sciences and Technology, Chonnam 
      National University, Gwangju, Republic of Korea.
FAU - Gang, Gil-Tae
AU  - Gang GT
FAU - Ryu, Dongryeol
AU  - Ryu D
FAU - Koh, Minseob
AU  - Koh M
FAU - Kim, Yo-Na
AU  - Kim YN
FAU - Kim, Su Sung
AU  - Kim SS
FAU - Park, Jinyoung
AU  - Park J
FAU - Kim, Yong-Hoon
AU  - Kim YH
FAU - Sim, Taebo
AU  - Sim T
FAU - Lee, In-Kyu
AU  - Lee IK
FAU - Choi, Cheol Soo
AU  - Choi CS
FAU - Park, Seung Bum
AU  - Park SB
FAU - Lee, Chul-Ho
AU  - Lee CH
FAU - Koo, Seung-Hoi
AU  - Koo SH
FAU - Choi, Hueng-Sik
AU  - Choi HS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130617
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Esrrg protein, mouse)
RN  - 0 (GSK5182)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Receptors, Estrogen)
RN  - 094ZI81Y45 (Tamoxifen)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cell Line
MH  - Gluconeogenesis/drug effects
MH  - Hepatocytes/drug effects/metabolism
MH  - Humans
MH  - Hypoglycemic Agents/*therapeutic use
MH  - Liver/*drug effects/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Polymerase Chain Reaction
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Estrogen/*agonists/*metabolism
MH  - Tamoxifen/*analogs & derivatives/pharmacokinetics/therapeutic use
PMC - PMC3749343
EDAT- 2013/06/19 06:00
MHDA- 2013/11/13 06:00
PMCR- 2014/09/01
CRDT- 2013/06/19 06:00
PHST- 2013/06/19 06:00 [entrez]
PHST- 2013/06/19 06:00 [pubmed]
PHST- 2013/11/13 06:00 [medline]
PHST- 2014/09/01 00:00 [pmc-release]
AID - db12-0946 [pii]
AID - 0946 [pii]
AID - 10.2337/db12-0946 [doi]
PST - ppublish
SO  - Diabetes. 2013 Sep;62(9):3093-102. doi: 10.2337/db12-0946. Epub 2013 Jun 17.