PMID- 20117072
OWN - NLM
STAT- MEDLINE
DCOM- 20100409
LR  - 20131121
IS  - 1096-0384 (Electronic)
IS  - 0003-9861 (Linking)
VI  - 496
IP  - 1
DP  - 2010 Apr 1
TI  - Metformin reverses hexokinase and 6-phosphofructo-1-kinase inhibition in skeletal 
      muscle, liver and adipose tissues from streptozotocin-induced diabetic mouse.
PG  - 53-60
LID - 10.1016/j.abb.2010.01.013 [doi]
AB  - The present work describes the effects of metformin on hexokinase (HK) and 
      phosphofructokinase (PFK) activities and localization in different tissues from 
      streptozotocin-induced diabetic mice. Diabetic mice present lower HK and PFK 
      activities (50%) in skeletal muscle, liver and adipose tissue, as compared with 
      control (P<0.05). Treatment with 250 mg/kg metformin reverses this pattern of 
      enzyme inhibition with concomitant reversal of hyperglycemia and 
      hypolactacidemia. Furthermore, the treatment increases the 
      cytoskeleton-associated PFK activity in skeletal muscle; this activity has been 
      described as an important mechanism for the enzyme activation. This effect might 
      be due to the increased phosphorylation of serine residues in the enzyme, a 
      modification which has been described to increase the interaction of PFK with 
      f-actin. The current work supports the hypothesis that metformin hypoglycemic 
      effects involve the activation of glycolysis through its regulatory enzymes, 
      which may be potential targets for the development of new hypoglycemic drugs.
CI  - 2010 Elsevier Inc. All rights reserved.
FAU - Da Silva, Daniel
AU  - Da Silva D
AD  - Laboratorio de Enzimologia e Controle do Metabolismo-LabECoM, Faculdade de 
      Farmacia, UFRJ, Brazil.
FAU - Zancan, Patricia
AU  - Zancan P
FAU - Coelho, Wagner Santos
AU  - Coelho WS
FAU - Gomez, Lilian Sales
AU  - Gomez LS
FAU - Sola-Penna, Mauro
AU  - Sola-Penna M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100201
PL  - United States
TA  - Arch Biochem Biophys
JT  - Archives of biochemistry and biophysics
JID - 0372430
RN  - 9100L32L2N (Metformin)
RN  - EC 2.7.1.1 (Hexokinase)
RN  - EC 2.7.1.11 (Phosphofructokinase-1)
SB  - IM
MH  - Adipose Tissue/*drug effects/metabolism
MH  - Animals
MH  - Biocatalysis/drug effects
MH  - Cell Line
MH  - Diabetes Mellitus, Experimental/drug therapy/*enzymology/metabolism
MH  - Drug Design
MH  - Glycolysis/drug effects
MH  - Hexokinase/*metabolism
MH  - Hypoglycemia/drug therapy
MH  - Liver/*drug effects/metabolism
MH  - Male
MH  - Metformin/*pharmacology/therapeutic use
MH  - Mice
MH  - Muscle, Skeletal/*drug effects/metabolism
MH  - Phosphofructokinase-1/*metabolism
MH  - Phosphorylation/drug effects
EDAT- 2010/02/02 06:00
MHDA- 2010/04/10 06:00
CRDT- 2010/02/02 06:00
PHST- 2009/12/14 00:00 [received]
PHST- 2010/01/22 00:00 [revised]
PHST- 2010/01/25 00:00 [accepted]
PHST- 2010/02/02 06:00 [entrez]
PHST- 2010/02/02 06:00 [pubmed]
PHST- 2010/04/10 06:00 [medline]
AID - S0003-9861(10)00037-8 [pii]
AID - 10.1016/j.abb.2010.01.013 [doi]
PST - ppublish
SO  - Arch Biochem Biophys. 2010 Apr 1;496(1):53-60. doi: 10.1016/j.abb.2010.01.013. 
      Epub 2010 Feb 1.