Diabetes-altered gene expression in rat skeletal muscle corrected by oral administration of vanadyl sulfate

Physiol Genomics. 2006 Aug 16;26(3):192-201. doi: 10.1152/physiolgenomics.00196.2005. Epub 2006 May 9.

Abstract

Treatment with vanadium, a representative of a class of antidiabetic compounds, alleviates diabetic hyperglycemia and hyperlipidemia. Oral administration of vanadium compounds in animal models and humans does not cause clinical symptoms of hypoglycemia, a common problem for diabetic patients with insulin treatment. Gene expression, using Affymetrix arrays, was examined in muscle from streptozotocin-induced diabetic and normal rats in the presence or absence of oral vanadyl sulfate treatment. This treatment affected normal rats differently from diabetic rats, as demonstrated by two-way ANOVA of the full array data. Diabetes altered the expression of 133 genes, and the expression of 30% of these genes dysregulated in diabetes was normalized by vanadyl sulfate treatment. For those genes, the ratio of expression in normal animals to the expression in diabetic animals showed a strong negative correlation with the ratio of expression in diabetic animals to the expression in diabetic animals treated with vanadyl sulfate (P = -0.85). The genes identified belong to six major metabolic functional groups: lipid metabolism, oxidative stress, muscle structure, protein breakdown and biosynthesis, the complement system, and signal transduction. The identification of oxidative stress genes, coupled with the known oxidative chemistry of vanadium, implicates reactive oxygen species in the action of this class of compounds. These results imply that early transition metals or compounds formed from their chemical interactions with other metabolites may act as general transcription modulators, a role not usually associated with this class of compounds.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Oral
  • Analysis of Variance
  • Animals
  • Blood Glucose / metabolism
  • Cholesterol / blood
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / physiopathology
  • Fatty Acids, Nonesterified / blood
  • Gene Expression / drug effects*
  • Gene Expression / genetics
  • Hyperglycemia / blood
  • Hyperglycemia / drug therapy
  • Hyperglycemia / physiopathology
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / pharmacology
  • Lipid Metabolism / genetics
  • Male
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism
  • Oligonucleotide Array Sequence Analysis / methods
  • Oxidative Stress / genetics
  • Rats
  • Rats, Wistar
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / genetics
  • Triglycerides / blood
  • Vanadium Compounds / administration & dosage
  • Vanadium Compounds / pharmacology*

Substances

  • Blood Glucose
  • Fatty Acids, Nonesterified
  • Hypoglycemic Agents
  • Triglycerides
  • Vanadium Compounds
  • vanadyl sulfate
  • Cholesterol