PMID- 17472435
OWN - NLM
STAT- MEDLINE
DCOM- 20070619
LR  - 20220409
IS  - 1549-1676 (Electronic)
IS  - 1549-1277 (Print)
IS  - 1549-1277 (Linking)
VI  - 4
IP  - 5
DP  - 2007 May
TI  - TXNIP regulates peripheral glucose metabolism in humans.
PG  - e158
LID - e158
AB  - BACKGROUND: Type 2 diabetes mellitus (T2DM) is characterized by defects in 
      insulin secretion and action. Impaired glucose uptake in skeletal muscle is 
      believed to be one of the earliest features in the natural history of T2DM, 
      although underlying mechanisms remain obscure. METHODS AND FINDINGS: We combined 
      human insulin/glucose clamp physiological studies with genome-wide expression 
      profiling to identify thioredoxin interacting protein (TXNIP) as a gene whose 
      expression is powerfully suppressed by insulin yet stimulated by glucose. In 
      healthy individuals, its expression was inversely correlated to total body 
      measures of glucose uptake. Forced expression of TXNIP in cultured adipocytes 
      significantly reduced glucose uptake, while silencing with RNA interference in 
      adipocytes and in skeletal muscle enhanced glucose uptake, confirming that the 
      gene product is also a regulator of glucose uptake. TXNIP expression is 
      consistently elevated in the muscle of prediabetics and diabetics, although in a 
      panel of 4,450 Scandinavian individuals, we found no evidence for association 
      between common genetic variation in the TXNIP gene and T2DM. CONCLUSIONS: TXNIP 
      regulates both insulin-dependent and insulin-independent pathways of glucose 
      uptake in human skeletal muscle. Combined with recent studies that have 
      implicated TXNIP in pancreatic beta-cell glucose toxicity, our data suggest that 
      TXNIP might play a key role in defective glucose homeostasis preceding overt 
      T2DM.
FAU - Parikh, Hemang
AU  - Parikh H
AD  - Department of Clinical Sciences, Diabetes and Endocrinology, Lund University, 
      University Hospital Malmo, Malmo, Sweden.
FAU - Carlsson, Emma
AU  - Carlsson E
FAU - Chutkow, William A
AU  - Chutkow WA
FAU - Johansson, Lovisa E
AU  - Johansson LE
FAU - Storgaard, Heidi
AU  - Storgaard H
FAU - Poulsen, Pernille
AU  - Poulsen P
FAU - Saxena, Richa
AU  - Saxena R
FAU - Ladd, Christine
AU  - Ladd C
FAU - Schulze, P Christian
AU  - Schulze PC
FAU - Mazzini, Michael J
AU  - Mazzini MJ
FAU - Jensen, Christine Bjorn
AU  - Jensen CB
FAU - Krook, Anna
AU  - Krook A
FAU - Bjornholm, Marie
AU  - Bjornholm M
FAU - Tornqvist, Hans
AU  - Tornqvist H
FAU - Zierath, Juleen R
AU  - Zierath JR
FAU - Ridderstrale, Martin
AU  - Ridderstrale M
FAU - Altshuler, David
AU  - Altshuler D
FAU - Lee, Richard T
AU  - Lee RT
FAU - Vaag, Allan
AU  - Vaag A
FAU - Groop, Leif C
AU  - Groop LC
FAU - Mootha, Vamsi K
AU  - Mootha VK
LA  - eng
SI  - GEO/GSE7146
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - PLoS Med
JT  - PLoS medicine
JID - 101231360
RN  - 0 (BCL6 protein, human)
RN  - 0 (Blood Glucose)
RN  - 0 (Carrier Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Insulin)
RN  - 0 (Proto-Oncogene Proteins c-bcl-6)
RN  - 0 (Qb-SNARE Proteins)
RN  - 0 (TXNIP protein, human)
SB  - IM
MH  - Adipocytes/cytology
MH  - Animals
MH  - Blood Glucose/genetics/*metabolism
MH  - Carrier Proteins/genetics/metabolism/*physiology
MH  - Cells, Cultured
MH  - DNA-Binding Proteins/genetics
MH  - Diabetes Mellitus, Type 2/genetics/metabolism/*physiopathology
MH  - Gene Expression Regulation/*physiology
MH  - Genetic Predisposition to Disease
MH  - Glucose Clamp Technique
MH  - Glucose Intolerance/genetics
MH  - Homeostasis/physiology
MH  - Humans
MH  - Hypoglycemic Agents/pharmacology
MH  - Insulin/pharmacology
MH  - Linkage Disequilibrium
MH  - Muscle, Skeletal/*metabolism/pathology
MH  - Polymerase Chain Reaction
MH  - Polymorphism, Single Nucleotide
MH  - Promoter Regions, Genetic/physiology
MH  - Protein Array Analysis
MH  - Proto-Oncogene Proteins c-bcl-6
MH  - Qb-SNARE Proteins/genetics
PMC - PMC1858708
COIS- Competing Interests: HT is employed at Novo Nordisk A/S, Denmark and owns a minor 
      amount of employers stock in this Company. LCG is a member of the editorial board 
      of PLoS Medicine.
EDAT- 2007/05/03 09:00
MHDA- 2007/06/20 09:00
PMCR- 2007/05/01
CRDT- 2007/05/03 09:00
PHST- 2006/11/21 00:00 [received]
PHST- 2007/03/01 00:00 [accepted]
PHST- 2007/05/03 09:00 [pubmed]
PHST- 2007/06/20 09:00 [medline]
PHST- 2007/05/03 09:00 [entrez]
PHST- 2007/05/01 00:00 [pmc-release]
AID - 06-PLME-RA-0918R1 [pii]
AID - 10.1371/journal.pmed.0040158 [doi]
PST - ppublish
SO  - PLoS Med. 2007 May;4(5):e158. doi: 10.1371/journal.pmed.0040158.