title: Metformin abolishes increased tumor (18)F-2-fluoro-2-deoxy-D-glucose uptake associated with a high energy diet.
abstract: 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 antineoplastic agent.
authors.affiliation: Department of Experimental Medicine, McGill University, Montreal, QC, Canada.
authors.forename: Haider
authors.initials: H
authors.lastname: Mashhedi
authors.forename: Marie-José
authors.initials: MJ
authors.lastname: Blouin
authors.forename: Mahvash
authors.initials: M
authors.lastname: Zakikhani
authors.forename: Stéphanie
authors.initials: S
authors.lastname: David
authors.forename: Yunhua
authors.initials: Y
authors.lastname: Zhao
authors.forename: Miguel
authors.initials: M
authors.lastname: Bazile
authors.forename: Elena
authors.initials: E
authors.lastname: Birman
authors.forename: Carolyn
authors.initials: C
authors.lastname: Algire
authors.forename: Antonio
authors.initials: A
authors.lastname: Aliaga
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Bedell
authors.forename: Michael
authors.initials: M
authors.lastname: Pollak
mesh_terms: D000821:Animal Feed; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001786:Blood Glucose / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000378:metabolism; D005462:Fluorine Radioisotopes / Q000032:analysis; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006946:Hyperinsulinism / Q000139:chemically induced; D007328:Insulin / Q000097:blood* / Q000494:pharmacology; D008687:Metformin / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D049268:Positron-Emission Tomography; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D001786:Blood Glucose; D005462:Fluorine Radioisotopes; D007328:Insulin; D019788:Fluorodeoxyglucose F18; D008687:Metformin; D011972:Receptor, Insulin; D005947:Glucose