Obesity and hyperglycemia have recently been identified as independent risk factors for the development of respiratory infections. Although the lung is a major organ to utilize glucose, the regulation of glucose transport in the healthy and diabetic lung has received little attention. We hypothesized that metformin would rescue diabetes-induced alterations of glucose transport in the lung. To test this hypothesis, we induced an insulin-resistant diabetic mouse model by feeding a high-fat diet for 16 weeks (n=10/group). A subset of mice was treated with metformin for 8 weeks. Protein content of class I glucose transporters (GLUTs -1, -2, -3, -4) and class III GLUTs (-8, -10, -12) was quantified by Western blotting in whole lung homogenates. Cell surface GLUTs were quantified using the biotinylated photolabeling technique. Glucose concentration in bronchoalveolar lavage (BAL) fluid was measured spectrophotometrically. After feeding a high-fat diet, mice became obese, mildly hyperglycemic, hyperinsulinemic, and insulin tolerant. Total protein content of GLUT4 and GLUT12 was significantly decreased in the lung of the insulin-resistant (IR) group (P <0.05). Following metformin treatment, protein content of GLUT4, but not GLUT12, was rescued in the lung of the treated IR mice (P <0.05). Cell-surface protein content of GLUT4 and GLUT8 was significantly decreased in the lung of IR mice, which was rescued in the treated group (P<0.05). IR mice demonstrated a trend towards a higher glucose concentration in the BAL fluid (P < 0.1). These novel findings suggest that 1) regulation of glucose transport is altered in the lung during obesity and hyperglycemia, potentially increasing the risk for pulmonary infection, and 2) metformin treatment rescues GLUT alterations in the lung of IR mice. Insights gained from this study could lead to the identification of significant metabolic therapeutic targets for diabetic patients affected by concurrent respiratory infections.


A. Campolo: None. Z. Maria: None. M. Hinsdale: None. L. Liu: None. V. Lacombe: None.


Harold Hamm Diabetes Center; National Institutes of Health

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