Translational Research: An unappreciated diabetogen in the American diet?
Researchers at the Duke Molecular Physiology Institute (DMPI) confirmed and expanded upon their earlier observation that beta-cell lines can take up and oxidize 5-hydroxymethyl-2-furfural (HMF), a dehydrated product of fructose. HMF is abundant in some ultra-processed foods. HMF is a suspected mutagen and carcinogen.
The DMPI research team proposes that the furan compound, 5-hydroxymethyl-2-furfural (HMF), which forms when hexoses such as glucose or fructose lose three water molecules during thermal food processing, might be an unrecognized dietary diabetogen. At higher doses, it is conceivable that HMF might be harmful to beta cells.
HMF was recently shown to be abundant in some commercial infant formulas. The team is currently examining HMF and its furoate catabolites in urines from neonates under care at Duke Children’s Hospital. The DMPI research team recently presented these findings at ENDO 2025.
In a previous experiment in the rat 832/13 beta-cell line, when cultures were shifted from low- (2.5 mM) to high-glucose media (12 mM), resulted in a large increase in intracellular 5-hydroxymethyl-2-furoic acid (Sumiki’s acid), a cellular oxidation product of HMF. This finding suggested that beta cells may be able to concentrate HMF from their environment and oxidize it to Sumiki’s acid.
In the present study, the transgenic rat beta-cell line, beta-G 49/206, which shares a close common ancestor with 832/13, was exposed to low-glucose (2.5 mM), high-glucose (12 mM), and a high-glucose buffer spiked with HMF (1 mM). Metabolites were measured by ultrahigh-pressure liquid chromatography / quadrupole, time-of-flight mass spectrometry (UHPLC / QToF MS) on an Agilent 1290 / 6546 system and by gas chromatography (GC) / MS on an Agilent 8890 / 5977B system.
Glucose concentrations were measured on a Beckman UniCel DxC 600 Synchron instrument. Mass spectrometry showed that the 49/206 beta cell line took up HMF and oxidized it to Sumiki’s acid. HMF-treated cells showed increased adenine, 6-methyluracil, spermidine, amino acids (lysine, phenylalanine, tyrosine), and lactate, and decreased Krebs cycle intermediates (succinate, fumarate, malate), suggesting a shift toward glycolysis – though that effect size was modest.
By deliberately spiking a glucose-secretion buffer with HMF, the DMPI research team confirmed earlier suspicions that transgenic rat beta-cell lines can take up HMF and oxidize it to Sumiki’s acid. HMF is abundant in ultra-processed foods, notably in high-fructose corn syrup. Given HMF’s known toxicity and the limited understanding of how Sumiki’s acid might impact beta-cell biology, the DMPI research team emphasizes that further investigation is warranted to determine whether physiologic levels of HMF and its oxidation products are potentially diabetogenic in the American diet.