Inflammation markers predict zinc transporter gene expression in women with type 2 diabetes mellitus

J Nutr Biochem. 2013 Sep;24(9):1655-61. doi: 10.1016/j.jnutbio.2013.02.006. Epub 2013 May 2.


The pathology of type 2 diabetes mellitus (DM) often is associated with underlying states of conditioned zinc deficiency and chronic inflammation. Zinc and omega-3 polyunsaturated fatty acids each exhibit anti-inflammatory effects and may be of therapeutic benefit in the disease. The present randomized, double-blind, placebo-controlled, 12-week trial was designed to investigate the effects of zinc (40 mg/day) and α-linolenic acid (ALA; 2 g/day flaxseed oil) supplementation on markers of inflammation [interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, C-reactive protein (CRP)] and zinc transporter and metallothionein gene expression in 48 postmenopausal women with type 2 DM. No significant effects of zinc or ALA supplementation were observed on inflammatory marker concentrations or fold change in zinc transporter and metallothionein gene expression. Significant increases in plasma zinc concentrations were observed over time in the groups supplemented with zinc alone or combined with ALA (P=.007 and P=.009, respectively). An impact of zinc treatment on zinc transporter gene expression was found; ZnT5 was positively correlated with Zip3 mRNA (P<.001) only in participants receiving zinc, while zinc supplementation abolished the relationship between ZnT5 and Zip10. IL-6 predicted the expression levels and CRP predicted the fold change of the ZnT5, ZnT7, Zip1, Zip7 and Zip10 mRNA cluster (P<.001 and P=.031, respectively). Fold change in the expression of metallothionein mRNA was predicted by TNF-α (P=.022). Associations among inflammatory cytokines and zinc transporter and metallothionein gene expression support an interrelationship between zinc homeostasis and inflammation in type 2 DM.

Keywords: ALA; C(P); C-reactive protein; CPT; CRP; DM; Gene expression; Inflammation; MT; PBMC; Randomized controlled trial; SLC; Type 2 diabetes mellitus; Zinc transporter; Zip; ZnT; Zrt- and Irt-like protein; cell preparation tube; crossing point; diabetes mellitus; metallothionein; n-3; omega-3; peripheral blood mononuclear cells; rRNA; ribosomal ribonucleic acid; solute carrier; zinc transporter; α-linolenic acid.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / blood
  • Biomarkers / blood*
  • Body Mass Index
  • C-Reactive Protein / metabolism
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / genetics*
  • Dietary Supplements*
  • Double-Blind Method
  • Female
  • Gene Expression / drug effects*
  • Humans
  • Inflammation / blood*
  • Interleukin-1beta / blood
  • Interleukin-6 / blood
  • Metallothionein / genetics
  • Metallothionein / metabolism
  • Middle Aged
  • Postmenopause / blood
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Tumor Necrosis Factor-alpha / blood
  • Zinc / administration & dosage
  • Zinc / blood
  • alpha-Linolenic Acid / administration & dosage
  • alpha-Linolenic Acid / blood


  • Anti-Inflammatory Agents
  • Biomarkers
  • Carrier Proteins
  • Interleukin-1beta
  • Interleukin-6
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • zinc-binding protein
  • alpha-Linolenic Acid
  • C-Reactive Protein
  • Metallothionein
  • Zinc