title: A newly synthetic chromium complex-chromium (D-phenylalanine)3 activates AMP-activated protein kinase and stimulates glucose transport.
abstract: We synthesized the chromium (phenylalanine)(3) [Cr(D-phe)(3)] by chelating chromium(III) with D-phenylalanine ligand in aqueous solution to improve the bioavailability of chromium, and reported that Cr(D-phe)(3) improved insulin sensitivity. AMP-activated protein kinase (AMPK) is a key mediator for glucose uptake and insulin sensitivity. To address the molecular mechanisms by which Cr(d-phe)(3) increases insulin sensitivity, we investigated whether Cr(D-phe)(3) stimulates glucose uptake via activation of AMPK signaling pathway. H9c2 myoblasts and isolated cardiomyocytes were treated with Cr(D-phe)(3) (25microM). Western blotting was used for signaling determination. The glucose uptake was determined by 2-deoxy-D-glucose-(3)H accumulation. HPLC measured concentrations of AMP. The mitochondrial membrane potential (Deltapsi) was detected by JC-1 fluorescence assay. Cr(D-phe)(3) stimulated the phosphorylation of alpha catalytic subunit of AMPK at Thr(172), as well the downstream targets of AMPK, acetyl-CoA carboxylase (ACC, Ser(212)) and eNOS (Ser(1177)). Moreover, Cr(D-phe)(3) significantly stimulated glucose uptake in both H9c2 cells and cardiomyocytes. AMPK inhibitor compound C (10microM) dramatically inhibited the glucose uptake stimulated by Cr(D-phe)(3), while it did not affect insulin stimulation of glucose uptake. Furthermore, in vivo studies showed that Cr(D-phe)(3) also activated cardiac AMPK signaling pathway. The increase of cardiac AMP concentration and the decrease of mitochondrial membrane potential (Deltapsi) may contribute to the activation of AMPK induced by Cr(D-phe)(3). Cr(D-phe)(3) is a novel compound that activates AMPK signaling pathway, which contributes to the regulation of glucose transport during stress conditions that may be associated the role of AMPK in increasing insulin sensitivity.
authors.affiliation: Department of Cardiology, Shandong Provincial Hospital, Shandong University, 324 Jingwuweiqi Road, Jinan 250021, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
authors.forename: Jingying
authors.initials: J
authors.lastname: Wang
authors.forename: Heng
authors.initials: H
authors.lastname: Ma
authors.forename: Yao
authors.initials: Y
authors.lastname: Xiao
authors.forename: Leilei
authors.initials: L
authors.lastname: He
authors.forename: Chao
authors.initials: C
authors.lastname: Tong
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Wang
authors.forename: Qiusheng
authors.initials: Q
authors.lastname: Zheng
authors.forename: E Kurt
authors.initials: EK
authors.lastname: Dolence
authors.forename: Sreejayan
authors.initials: S
authors.lastname: Nair
authors.forename: Jun
authors.initials: J
authors.lastname: Ren
authors.forename: Ji
authors.initials: J
authors.lastname: Li
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D017608:Chromium Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology; D051379:Mice; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D017608:Chromium Compounds; D009942:Organometallic Compounds; C512471:chromium (D-Phenylalanine)3; D010649:Phenylalanine; D055372:AMP-Activated Protein Kinases; D005947:Glucose