PMID- 27163678
OWN - NLM
STAT- MEDLINE
DCOM- 20170705
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 11
IP  - 5
DP  - 2016
TI  - MicroRNA-194 Modulates Glucose Metabolism and Its Skeletal Muscle Expression Is 
      Reduced in Diabetes.
PG  - e0155108
LID - 10.1371/journal.pone.0155108 [doi]
LID - e0155108
AB  - BACKGROUND: The regulation of microRNAs (miRNAs) at different stages of the 
      progression of type 2 diabetes mellitus (T2DM) and their role in glucose 
      homeostasis was investigated. METHODS: Microarrays were used to assess miRNA 
      expression in skeletal muscle biopsies taken from healthy individuals and 
      patients with pre-diabetes or T2DM, and insulin resistant offspring of rat dams 
      fed a high fat diet during pregnancy. RESULTS: Twenty-three miRNAs were 
      differentially expressed in patients with T2DM, and 7 in the insulin resistant 
      rat offspring compared to their controls. Among these, only one miRNA was 
      similarly regulated: miR-194 expression was significantly reduced by 25 to 50% in 
      both the rat model and in human with pre-diabetes and established diabetes. 
      Knockdown of miR-194 in L6 skeletal muscle cells induced an increase in basal and 
      insulin-stimulated glucose uptake and glycogen synthesis. This occurred in 
      conjunction with an increased glycolysis, indicated by elevated lactate 
      production. Moreover, oxidative capacity was also increased as we found an 
      enhanced glucose oxidation in presence of the mitochondrial uncoupler FCCP. When 
      miR-194 was down-regulated in vitro, western blot analysis showed an increased 
      phosphorylation of AKT and GSK3beta in response to insulin, and an increase in 
      expression of proteins controlling mitochondrial oxidative phosphorylation. 
      CONCLUSIONS: Type 2 diabetes mellitus is associated with regulation of several 
      miRNAs in skeletal muscle. Interestingly, miR-194 was a unique miRNA that 
      appeared regulated across different stages of the disease progression, from the 
      early stages of insulin resistance to the development of T2DM. We have shown 
      miR-194 is involved in multiple aspects of skeletal muscle glucose metabolism 
      from uptake, through to glycolysis, glycogenesis and glucose oxidation, 
      potentially via mechanisms involving AKT, GSK3 and oxidative phosphorylation. 
      MiR-194 could be down-regulated in patients with early features of diabetes as an 
      adaptive response to facilitate tissue glucose uptake and metabolism in the face 
      of insulin resistance.
FAU - Latouche, Celine
AU  - Latouche C
AD  - Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
FAU - Natoli, Alaina
AU  - Natoli A
AD  - Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
FAU - Reddy-Luthmoodoo, Medini
AU  - Reddy-Luthmoodoo M
AD  - Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
FAU - Heywood, Sarah E
AU  - Heywood SE
AD  - Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
FAU - Armitage, James A
AU  - Armitage JA
AD  - School of Medicine (Optometry), Deakin University, Waurn Ponds, Victoria, 
      Australia.
FAU - Kingwell, Bronwyn A
AU  - Kingwell BA
AD  - Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160510
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Insulin)
RN  - 0 (MIRN194 microRNA, human)
RN  - 0 (MIRN194 microRNA, rat)
RN  - 0 (MicroRNAs)
RN  - 9005-79-2 (Glycogen)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Diabetes Mellitus, Type 2/*genetics/metabolism/pathology
MH  - Diet, High-Fat/adverse effects
MH  - Disease Models, Animal
MH  - Female
MH  - Gene Expression Regulation
MH  - Glucose/*metabolism
MH  - Glycogen/metabolism
MH  - Glycogen Synthase Kinase 3/genetics/metabolism
MH  - Humans
MH  - Insulin/*metabolism
MH  - Insulin Resistance
MH  - Male
MH  - Mice, Inbred C57BL
MH  - MicroRNAs/*genetics/metabolism
MH  - Mitochondria/metabolism
MH  - Muscle, Skeletal/*metabolism/pathology
MH  - Myoblasts/metabolism/pathology
MH  - Oxidative Phosphorylation
MH  - Prediabetic State/etiology/*genetics/metabolism/pathology
MH  - Proto-Oncogene Proteins c-akt/genetics/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction
PMC - PMC4862646
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2016/05/11 06:00
MHDA- 2017/07/06 06:00
PMCR- 2016/05/10
CRDT- 2016/05/11 06:00
PHST- 2015/11/25 00:00 [received]
PHST- 2016/04/25 00:00 [accepted]
PHST- 2016/05/11 06:00 [entrez]
PHST- 2016/05/11 06:00 [pubmed]
PHST- 2017/07/06 06:00 [medline]
PHST- 2016/05/10 00:00 [pmc-release]
AID - PONE-D-15-49826 [pii]
AID - 10.1371/journal.pone.0155108 [doi]
PST - epublish
SO  - PLoS One. 2016 May 10;11(5):e0155108. doi: 10.1371/journal.pone.0155108. 
      eCollection 2016.