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Hyperglycaemia Elevates Epithelial Lactate Secretion and Alters pH of Airway Surface Liquid
Author(s) -
Garnett James,
Baker Emma,
Baines Deborah
Publication year - 2015
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.29.1_supplement.1014.4
Subject(s) - medicine , endocrinology , bronchoalveolar lavage , chemistry , lung , respiratory system
Glucose in airway surface liquid (ASL) is normally ~0.4 mM, but rises (up to 4mM) when blood glucose is elevated (hyperglycaemia) and in respiratory disease, making the lung more susceptible to respiratory infection. We investigated whether hyperglycaemia also modified ASL lactate concentrations and the pH, of bronchoalveolar lavage (BAL) from wild type (WT) and glucokinase deficient GK+/‐ mice, and the ASL of primary human bronchial epithelial cells (HBE) and cell lines H441 & Calu3, cultured at air‐liquid‐interface. Blood glucose was elevated in GK+/‐ compared to WT mice (WT= 9.4±0.2 mM, GK+/‐= 15.1±0.6 mM; p<0.001, n=12). BAL (but not blood) lactate was elevated in GK+/‐ mice (0.052±0.002 to 0.09±0.008 mM; p<0.05, n=6) and there was a correlation between blood glucose and BAL lactate. There was no difference in BAL inflammatory cell counts between GK+/‐ and WT mice (n=6), indicating another source of lactate in GK+/‐ lung. In vitro , elevation of basolateral glucose from 5 to 15 mM increased ASL lactate concentrations (Calu‐3= 2.2±0.7 to 7.1±1.2 mM; H441= 3.7±0.3 to 8.3±1.0 mM; HBE= 0.51±0.11 to 2.2±0.12 mM; P<0.05, n=7‐13) after 6 hours, and also produced an alkalinisation of Calu‐3 and HBE monolayer ASL, but acidified Cystic Fibrosis (CF) HBE ASL. This acidification could be mimicked in normal HBE monolayers by removing HCO 3 ‐ from the bathing solution. Inhibition of MCT1/2 with AR‐C155858 (100 nM) partially overcame the effects of hyperglycaemia on ASL lactate and pH. These data indicate that hyperglycaemia increases lactate in ASL via secretion through epithelial MCT1/2 transporters. Also, the airway epithelium compensates for MCT driven H + secretion by secreting HCO 3 ‐ , which is defective in CF epithelia. Funded by MRC‐MICA MR/K012770/1.