title: Zinc transporter gene expression and glycemic control in post-menopausal women with Type 2 diabetes mellitus.
abstract: Type 2 diabetes mellitus (DM) is associated often with underlying zinc deficiency and nutritional supplements such as zinc may be of therapeutic benefit in the disease. In a randomized, double-blind, placebo-controlled, 12-week trial in postmenopausal women (n=48) with Type 2 DM we investigated the effects of supplementation with zinc (40mg/d) and flaxseed oil (FSO; 2g/d) on the gene expression of zinc transporters (ZnT1, ZnT5, ZnT6, ZnT7, ZnT8, Zip1, Zip3, Zip7, and Zip10) and metallothionein (MT-1A, and MT-2A), and markers of glycemic control (glucose, insulin, glycosylated hemoglobin [HbA1c]). The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. No significant effects of zinc or FSO supplementation were observed on glycemic marker concentrations, HOMA-IR or fold change over 12 weeks in zinc transporter and metallothionein gene expression. In multivariate analysis, the change over 12 weeks in serum glucose concentrations (P=0.001) and HOMA-IR (P=0.001) predicted the fold change in Zip10. In secondary analysis, marginal statistical significance was observed with the change in both serum glucose concentrations (P=0.003) and HOMA-IR (P=0.007) being predictive of the fold change in ZnT6. ZnT8 mRNA expression was variable; HbA1c levels were higher (P=0.006) in participants who exhibited ZnT8 expression compared to those who did not. The significant predictive relationships between Zip10, ZnT6, serum glucose and HOMA-IR are preliminary, as is the relationship between HbA1c and ZnT8; nevertheless the observations support an association between Type 2 DM and zinc homeostasis that requires further exploration.
authors.affiliation: Discipline of Nutrition & Metabolism, School of Molecular Bioscience, University of Sydney, NSW 2006, Australia.
authors.forename: Meika
authors.initials: M
authors.lastname: Foster
authors.affiliation: Discipline of Nutrition & Metabolism, School of Molecular Bioscience, University of Sydney, NSW 2006, Australia.
authors.forename: Anna
authors.initials: A
authors.lastname: Chu
authors.affiliation: Department of Statistics, Macquarie University, NSW 2109, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Petocz
authors.affiliation: Discipline of Nutrition & Metabolism, School of Molecular Bioscience, University of Sydney, NSW 2006, Australia. Electronic address: samir.samman@otago.ac.nz.
authors.forename: Samir
authors.initials: S
authors.lastname: Samman
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000187:drug effects*; D002352:Carrier Proteins / Q000235:genetics*; D027682:Cation Transport Proteins / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000235:genetics*; D005260:Female; D006801:Humans; D008043:Linseed Oil / Q000494:pharmacology*; D008875:Middle Aged; D017698:Postmenopause; D015032:Zinc / Q000494:pharmacology*; D000075703:Zinc Transporter 8
chemical_list: D001786:Blood Glucose; D002352:Carrier Proteins; D027682:Cation Transport Proteins; C504822:SLC30A6 protein, human; C492522:SLC30A8 protein, human; D000075703:Zinc Transporter 8; C017800:zinc-binding protein; D008043:Linseed Oil; D015032:Zinc
keywords: Gene expression; Glucose; Insulin; Type 2 diabetes mellitus; Zinc transporter