Linked Life Data

12769787

Source:http://linkedlifedata.com/resource/pubmed/id/12769787

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2003-5-28
pubmed:abstractText
Although a number of assessments disagree, the preponderance of the evidence indicates that the major therapeutic action of metformin in type 2 diabetes (DM2) is on the liver, and glucose production (EGP) in particular. At the level of this organ, the actions of metformin can be characterized as pleiotropic. The major questions addressed here are therefore: (i) the methodological aspects of the determination of glucose fluxes: when glucose production is not found to be elevated in type 2 diabetes, it is not surprising that little action of metformin on this flux is found. The issues of populations examined, experimental protocols, and quantitative methods of flux determination are important in answering this question. Early morning EGP is increased and constitutes a valid target for metformin. (ii) the multiple targets of metformin: metformin acts at a number of sites and interacts with metabolites and hormones. Some of these actions may be expressed at different doses. Although their net effect is therapeutic, not all are oriented towards lowering hyperglycemia, perhaps explaining the more modest effect of this drug than could be anticipated from individual actions. Sites of metformin action can therefore be considered as a compilation of valid therapeutic targets in DM2. Gluconeogenesis, glycogenolysis and glycogen synthesis can be altered by metformin, although in vivo, this also depends on the methodology. Component processes from substrate supply and liver uptake, through a number of glucogenic enzymes, as well as glycogen synthase and phosphorylase have all been shown to be affected. (iii) unifying concepts: reported actions of metformin on the mitochondrial respiratory chain, free fatty acid metabolism, AMP-activated protein kinase, and on membrane proteins directly may all explain subsets of actions that are seen, providing more integrated targets for consideration in the therapy of DM2.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1568-0088
pubmed:author
pubmed:issnType
Print
pubmed:volume
3
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
151-69
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Metformin and its liver targets in the treatment of type 2 diabetes.
pubmed:affiliation
Department of Medicine, Ottawa Hospital and University of Ottawa, ON, Canada. jradziuk@ohri.ca
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't