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Reduced transepithelial glucose movement in metformin‐treated airways correlates with inhibition of hyperglycemia‐induced bacterial growth
Author(s) -
Garnett James P,
Baker Emma H,
Tregoning John S,
Baines Deborah L
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1148.22
Subject(s) - metformin , medicine , endocrinology , paracellular transport , staphylococcus aureus , glucose uptake , biguanide , glucose transporter , chemistry , insulin , biology , bacteria , biochemistry , permeability (electromagnetism) , membrane , genetics
Raised blood glucose elevates airway glucose and promotes respiratory infection. We investigated the effect of metformin on airway Staphylococcus aureus growth. Inoculation of H441 monolayers with 5×10 5 CFU/cm 2 S. aureus (8325–4) for 7h reduced transepithelial electrical resistance and enhanced paracellular glucose flux (assessed using 14 C‐L‐glucose; P<0.05 and P<0.0001 respectively, n=8). 1 mM metformin attenuated these changes (P<0.001). Apical S. aureus growth increased with basolateral glucose concentration (10–40 mM). Growth was impaired by metformin pre‐treatment (P<0.05, n=9). Metformin had no effect on H441 monolayer 14 C‐D‐glucose uptake or S. aureus growth in microbial culture. 6–10 week old db/db mice (leptin receptor deficient; blood glucose 17.7±1.6 mM, n=10) intranasally inoculated with 10 7 CFU S. aureus had 382±57% more CFU in their bronchoalveolar lavage after 24h (P<0.001, n=10), compared to WT mice (C57BL/6; blood glucose 7.4±0.1 mM, n=10). Treatment with 40 mg/kg metformin for two days prior to infection reduced S. aureus CFU in db/db mice by 50±9% (P<0.01, n=10) compared to PBS‐treated db/db mice, without reducing blood glucose levels. Metformin reduced paracellular glucose flux across ex vivo mouse tracheas by 40±5% (P<0.05, n=3). These data indicate that metformin inhibits hyperglycaemia‐induced S. aureus growth by reducing paracellular diffusion of glucose into the airways.