31 Martineau, L. C. Couture, A. Spoor, D. Benhaddou-Andaloussi, A. Harris, C. Meddah, B. Leduc, C. Burt, A. Vuong, T. Mai Le, P. Prentki, M. Bennett, S. A. Arnason, J. T. Haddad, P. S. 2006 Phytomedicine 13 9-10 612-23 Nov 0944-7113 (Print) 16979328 Plant Extracts/chemistry/pharmacology Mice Lipid Metabolism/drug effects Insulin/metabolism Hypoglycemic Agents/analysis/*pharmacology Glucose/metabolism/toxicity Deoxyglucose/metabolism Cytoprotection/drug effects Cell Proliferation/drug effects Cell Line Blueberry Plant/*chemistry Animals 3T3 Cells Incidence of type II diabetes is rapidly increasing worldwide. In order to identify complementary or alternative approaches to existing medications, we studied anti-diabetic properties of Vaccinium angustifolium Ait., a natural health product recommended for diabetes treatment in Canada. Ethanol extracts of root, stem, leaf, and fruit were tested at 12.5 microg/ml for anti-diabetic activity in peripheral tissues and pancreatic beta cells using a variety of cell-based bioassays. Specifically, we assessed: (1) deoxyglucose uptake in differentiated C2C12 muscle cells and 3T3-L1 adipocytes; (2) glucose-stimulated insulin secretion (GSIS) in beta TC-tet pancreatic beta cells; (3) beta cell proliferation in beta TC-tet cells; (4) lipid accumulation in differentiating 3T3-L1 cells; (5) protection against glucose toxicity in PC12 cells. Root, stem, and leaf extracts significantly enhanced glucose transport in C2C12 cells by 15-25% in presence and absence of insulin after 20 h of incubation; no enhancement resulted from a 1 h exposure. In 3T3 cells, only the root and stem extracts enhanced uptake, and this effect was greater after 1 h than after 20 h; uptake was increased by up to 75% in absence of insulin. GSIS was potentiated by a small amount in growth-arrested beta TC-tet cells incubated overnight with leaf or stem extract. However, fruit extracts were found to increase 3H-thymidine incorporation in replicating beta TC-tet cells by 2.8-fold. Lipid accumulation in differentiating 3T3-L1 cells was accelerated by root, stem, and leaf extracts by as much as 6.5-fold by the end of a 6-day period. Stem, leaf, and fruit extracts reduced apoptosis by 20-33% in PC12 cells exposed to elevated glucose for 96 h. These results demonstrate that V. angustifolium contains active principles with insulin-like and glitazone-like properties, while conferring protection against glucose toxicity. Enhancement of proliferation in beta cells may represent another potential anti-diabetic property. Extracts of the Canadian blueberry thus show promise for use as a complementary anti-diabetic therapy. Journal ArticleResearch Support, Non-U.S. Gov'tGermanyinternational journal of phytotherapy and phytopharmacology http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16979328