Altered Pulmonary Glucose Transport Is Restored by Metformin Treatment in an Obese Type 2 Diabetic Animal Model

Background/Objectives: Obesity and hyperglycemia predispose patients to respiratory infections. Although the lung is a major organ to utilize glucose, pulmonary glucose homeostasis in type 2 diabetic (T2Dx) subjects remains poorly characterized. We hypothesized that pulmonary glucose transport would be altered during T2Dx, which would be rescued with long-term metformin treatment. Methods: T2Dx was induced by feeding mice a high-fat diet for 16 weeks, with metformin treatment administered during the final 8 weeks. Results: Glucose transporter (GLUT) protein expression and trafficking was quantified by Western blotting and the biotinylated photolabeling assay, respectively. T2Dx mice exhibited obesity, and increased glucose levels in blood and bronchoalveolar lavage (BAL) fluid. T2Dx also significantly decreased protein expression of GLUTs from Class I (i.e., GLUT-2 and -4) and class III (i.e., GLUT-10 and -12) isoforms in lung. Metformin treatment restored the protein expression of GLUT-2, -4, and -10, but not GLUT-12. Pulmonary cell surface expression of GLUT-4 and -8 was also significantly reduced in T2Dx mice and rescued by metformin. Conclusions: These findings suggest that alterations in pulmonary GLUT expression and trafficking during diabetes could contribute to the elevated airway glucose levels and severity of respiratory infections. Metformin treatment restored pulmonary glucose transport during T2Dx.