Glucose lowering activity by oral administration of bis(allixinato)oxidovanadium(iv) complex in streptozotocin-induced diabetic mice and gene expression profiling in their skeletal muscles

文献情報

出版日 2008-11-18

DOI 10.1039/B815384C

インパクトファクター 0

著者

Yusuke Adachi, Megumi Machida, Masakazu Hattori

要旨

Vanadyl(IV) complexes are anti-diabetogenic agents. Intra-peritoneal administration of bis(allixinato)oxidovanadium(IV) [VO(alx)2] lowers high blood glucose levels in animal models of type 1 and type 2 diabetes. We have examined whether oral administration of VO(alx)2 restores impaired activation in signaling cascades related to glucose metabolism and insulin action, and alters gene expression in the skeletal muscles of streptozotocin (STZ)-induced diabetic mice (STZ-diabetic mice). We report here that daily oral administration of VO(alx)2 lowered high blood glucose levels in the STZ-diabetic mice. The oral administration of VO(alx)2 enhanced phosphorylation of Akt and glycogen synthase kinase-3β (GSK3β), located downstream of the insulin receptor cascade in the skeletal muscles. We analyzed gene expression in the muscles of the diabetic mice before and after insulin or VO(alx)2 treatment. Treating the diabetic mice with insulin or VO(alx)2 normalized the gene expression levels of 152 down-regulated and 11 up-regulated genes, and especially the up-regulation of Cyp2E1 and FoxO1 in the muscles of the diabetic mice. The insulin-mimetic effects of VO(alx)2 in the STZ-induced diabetic mice may be due to the enhancement of protein phosphorylation leading to the activation or inactivation of the transcriptional machinery. Our findings suggest that the insulin-mimetic effects of VO(alx)2 in diabetes may be due to changes in the protein phosphorylations and their gene expression levels.

掲載誌

Metallomics

CiteScore: 7

自己引用率: 6.9%

年間論文数: 77

Metallomics publishes cutting-edge investigations aimed at elucidating the identification, distribution, dynamics, role and impact of metals and metalloids in biological systems. Studies that address the “what, where, when, how and why” of these inorganic elements in cells, tissues, organisms, and various environmental niches are welcome, especially those employing multidisciplinary approaches drawn from the analytical, bioinorganic, medicinal, environmental, biophysical, cell biology, plant biology and chemical biology communities. We are particularly interested in articles that enhance our chemical and/or physical understanding of the molecular mechanisms of metal-dependent life processes, and those that probe the common space between metallomics and other ‘omics approaches to uncover new insights into biological processes. Metallomics seeks to position itself at the forefront of those advances in analytical chemistry destined to clarify the enormous complexity of biological systems. As such, we particularly welcome those papers that outline cutting-edge analytical technologies, e.g., in the development and application of powerful new imaging, spectroscopic and mass spectrometric modalities. Work that describes new insights into metal speciation, trafficking and dynamics in complex systems or as a function of microenvironment are also strongly encouraged. Studies that examine the interconnectivity of metal-dependent processes with systems level responses relevant to organismal health or disease are also strongly encouraged, for example those that probe the effect of chemical exposure on metal homeostasis or the impact of metal-based drugs on cellular processes.