Metformin abolishes increased tumor ( 18) F-2-Fluoro-2-Deoxy-D-Glucose uptake associated with a high-energy diet.
Summary of "Metformin abolishes increased tumor ( 18) F-2-Fluoro-2-Deoxy-D-Glucose uptake associated with a high-energy diet."
Insulin regulates glucose uptake by normal tissues. Although there is evidence that certain cancers are growth-stimulated by insulin, the possibility that insulin influences tumor glucose uptake as assessed by ( 18) F-2-Fluoro-2-Deoxy-D-Glucose Positron Emission Tomography (FDG-PET) has not been studied in detail. We present a model of diet-induced hyperinsulinemia associated with increased insulin receptor activation in neoplastic tissue, and with increased tumor FDG-PET image intensity. Metformin abolished the diet-induced increases in serum insulin level, tumor insulin receptor activation, and tumor FDG uptake associated with the high-energy diet, but had no effect on these measurements in mice on a control diet. These findings provide the first functional imaging correlate of the well-known adverse effect of caloric excess on cancer outcome. They demonstrate that for a subset of neoplasms, diet and insulin are variables that affect tumor FDG uptake, and have implications for design of clinical trials of metformin as an anti-neoplastic agent.
Affiliation
Department of Experimental Medicine; McGill University and Cancer Prevention Center; SMBD-Jewish General Hospital; McGill University; Montreal, QC, Canada.
Journal Details
This article was published in the following journal.
Name: Cell cycle (Georgetown, Tex.)
ISSN: 1551-4005
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21811094
- DOI: http://dx.doi.org/
Medical and Biotech [MESH] Definitions
Metformin
A biguanide hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. Metformin improves glycemic control by improving insulin sensitivity and decreasing intestinal absorption of glucose. (From Martindale, The Extra Pharmacopoeia, 30th ed, p289)
Glucose Transporter Type 4
A glucose transport protein found in mature MUSCLE CELLS and ADIPOCYTES. It promotes transport of glucose from the BLOOD into target TISSUES. The inactive form of the protein is localized in CYTOPLASMIC VESICLES. In response to INSULIN, it is translocated to the PLASMA MEMBRANE where it facilitates glucose uptake.
Heparin Lyase
An enzyme of the isomerase class that catalyzes the eliminative cleavage of polysaccharides containing 1,4-linked D-glucuronate or L-iduronate residues and 1,4-alpha-linked 2-sulfoamino-2-deoxy-6-sulfo-D-glucose residues to give oligosaccharides with terminal 4-deoxy-alpha-D-gluc-4-enuronosyl groups at their non-reducing ends. (From Enzyme Nomenclature, 1992) EC 4.2.2.7.
Deoxyglucose
2-Deoxy-D-arabino-hexose. An antimetabolite of glucose with antiviral activity.
3-o-methylglucose
A non-metabolizable glucose analogue that is not phosphorylated by hexokinase. 3-O-Methylglucose is used as a marker to assess glucose transport by evaluating its uptake within various cells and organ systems. (J Neurochem 1993;60(4):1498-504)
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