Genes & Nutrition

, Volume 7, Issue 3, pp 459–469 | Cite as

Benfotiamine increases glucose oxidation and downregulates NADPH oxidase 4 expression in cultured human myotubes exposed to both normal and high glucose concentrations

  • D. A. Fraser
  • N. P. Hessvik
  • N. Nikolić
  • V. Aas
  • K. F. Hanssen
  • S. K. Bøhn
  • G. H. Thoresen
  • A. C. Rustan
Research Paper

Abstract

The aim of the present work was to study the effects of benfotiamine (S-benzoylthiamine O-monophosphate) on glucose and lipid metabolism and gene expression in differentiated human skeletal muscle cells (myotubes) incubated for 4 days under normal (5.5 mM glucose) and hyperglycemic (20 mM glucose) conditions. Myotubes established from lean, healthy volunteers were treated with benfotiamine for 4 days. Glucose and lipid metabolism were studied with labeled precursors. Gene expression was measured using real-time polymerase chain reaction (qPCR) and microarray technology. Benfotiamine significantly increased glucose oxidation under normoglycemic (35 and 49% increase at 100 and 200 μM benfotiamine, respectively) as well as hyperglycemic conditions (70% increase at 200 μM benfotiamine). Benfotiamine also increased glucose uptake. In comparison, thiamine (200 μM) increased overall glucose metabolism but did not change glucose oxidation. In contrast to glucose, mitochondrial lipid oxidation and overall lipid metabolism were unchanged by benfotiamine. The expression of NADPH oxidase 4 (NOX4) was significantly downregulated by benfotiamine treatment under both normo- and hyperglycemic conditions. Gene set enrichment analysis (GSEA) showed that befotiamine increased peroxisomal lipid oxidation and organelle (mitochondrial) membrane function. In conclusion, benfotiamine increases mitochondrial glucose oxidation in myotubes and downregulates NOX4 expression. These findings may be of relevance to type 2 diabetes where reversal of reduced glucose oxidation and mitochondrial capacity is a desirable goal.

Keywords

Benfotiamine Thiamine Myotubes Diabetes Hyperglycemia 

Abbreviations

NAD

Nicotinamide adenine dinucleotide

NADPH

Nicotinamide adenine dinucleotide phosphate

NOX

Nicotinamide adenine dinucleotide phosphate oxidase

TK

Transketolase

PPP

Pentose phosphate pathway

PDH

Pyruvate dehydrogenase

KDH

Ketoglutarate dehydrogenase

TCA

Tricarboxylic acid

IMTG

Intramyocellular triacylglycerol

SPA

Scintillation proximity assay

NG

Normoglycemic

HG

Hyperglycemic

MDK

Growth factor midkine

TMP

Thiamine monophosphate

TPP

Thiamine diphosphate

RFC

Reduced folate carrier

OXPHOS

Oxidative phosphorylation

Supplementary material

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Supplementary material 1 (XLS 61 kb)
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Supplementary material 2 (XLS 47 kb)
12263_2011_252_MOESM3_ESM.xlsx (1.6 mb)
Supplementary material 3 (XLSX 1588 kb)

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • D. A. Fraser
    • 1
  • N. P. Hessvik
    • 2
  • N. Nikolić
    • 2
  • V. Aas
    • 3
  • K. F. Hanssen
    • 4
  • S. K. Bøhn
    • 5
  • G. H. Thoresen
    • 2
  • A. C. Rustan
    • 2
  1. 1.Diabetes Research CentreOslo University HospitalOsloNorway
  2. 2.Department of Pharmaceutical Biosciences, School of PharmacyUniversity of OsloOsloNorway
  3. 3.Faculty of Health SciencesOslo University CollegeOsloNorway
  4. 4.Department of EndocrinologyOslo University HospitalOsloNorway
  5. 5.Department of Nutrition, Faculty of Medicine, Institute of Basic Medical SciencesUniversity of OsloOsloNorway

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