title: Regulation of liver cell glucose homeostasis by dehydroabietic acid, abietic acid and squalene isolated from balsam fir (Abies balsamea (L.) Mill.) a plant of the Eastern James Bay Cree traditional pharmacopeia.
abstract: In our previous study, Abies balsamea (L.) Mill., a plant used in Cree traditional medicine, had a strong effect on the regulation of glucose homeostasis in liver cells. This study aimed to isolate and identify its active constituents using a bioassay-guided fractionation approach as well as to elucidate their mechanism(s) of action. The effect of the crude extract and its constituents was evaluated on the activity of Glucose-6-Phosphatase (G6Pase) and Glycogen Synthase (GS) and phosphorylation of three kinases, AMP-activated protein kinase (AMPK), Akt and Glycogen Synthase Kinase-3 (GSK-3). Three compounds, abietic acid, dehydroabietic acid and squalene, were isolated from the most active fraction in the bioassays (hexane). The compounds were able to decrease the activity of G6Pase and to stimulate GS. Their effect on G6Pase activity involved both Akt and AMPK phosphorylation with significant correlations between insulin-dependent and -independent pathways and the bioassay. In addition, the compounds were able to stimulate GS through GSK-3 phosphorylation with a significant correlation between the signaling pathway and the bioassay. Dehydroabietic acid stood out for its strongest effect in all the experiments close to that of the crude extract. These compounds may have potential applications in the treatment of type 2 diabetes and insulin resistance.
authors.affiliation: Natural Health Products and Metabolic Diseases Laboratory, Dept. of Pharmacology, Université de Montréal, Montreal, QC, Canada; Canadian Institutes of Health Research Team in Aboriginal Antidiabetic Medicines and Montreal Diabetes Research Center, Canada.
authors.forename: Abir
authors.initials: A
authors.lastname: Nachar
authors.affiliation: Canadian Institutes of Health Research Team in Aboriginal Antidiabetic Medicines and Montreal Diabetes Research Center, Canada; Laboratory for the Analysis of Natural and Synthetic Environmental Toxins, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Ammar
authors.initials: A
authors.lastname: Saleem
authors.affiliation: Canadian Institutes of Health Research Team in Aboriginal Antidiabetic Medicines and Montreal Diabetes Research Center, Canada; Laboratory for the Analysis of Natural and Synthetic Environmental Toxins, University of Ottawa, Ottawa, ON, Canada.
authors.forename: John T
authors.initials: JT
authors.lastname: Arnason
authors.affiliation: Natural Health Products and Metabolic Diseases Laboratory, Dept. of Pharmacology, Université de Montréal, Montreal, QC, Canada; Canadian Institutes of Health Research Team in Aboriginal Antidiabetic Medicines and Montreal Diabetes Research Center, Canada. Electronic address: pierre.haddad@umontreal.ca.
authors.forename: Pierre S
authors.initials: PS
authors.lastname: Haddad
mesh_terms: D028202:Abies / Q000737:chemistry*; D045784:Abietanes / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D045744:Cell Line, Tumor / Q000187:drug effects; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005947:Glucose / Q000378:metabolism*; D006006:Glycogen Synthase / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008519:Medicine, Traditional; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D013185:Squalene / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D045784:Abietanes; D010936:Plant Extracts; C013913:dehydroabietic acid; D013185:Squalene; D007770:L-Lactate Dehydrogenase; D006006:Glycogen Synthase; D005947:Glucose; C023710:abietic acid
keywords: AMPK; Abies balsamea; Akt; Balsam fir; GSK-3; Glucose-6-Phosphatase; Glycogen Synthase; Natural Health Product; Pinaceae; Traditional Aboriginal Medicine; Type 2 diabetes