Getting sweeter: new evidence for glucose transporters in specific cell types of the airway?

Abstract

New technologies such as single cell RNA sequencing (scRNAseq) has enabled identification of the mRNA transcripts expressed by individual cells. This review provides insight from recent scRNAseq studies, on the expression of glucose transporters in the epithelial cells of the airway epithelium from trachea to alveolus. The number of studies analysed was limited, not all reported the full range of glucose transporters and there were differences between cells freshly isolated from the airways and those grown in vitro. Furthermore, glucose transporter mRNA transcripts were expressed at lower levels than other epithelial marker genes. Nevertheless, these studies highlighted that there were differences in cellular expression of glucose transporters. GLUT1 was the most abundant of the broadly expressed transporters that included GLUT8, 10 and 13. GLUT9 transcripts were more common in basal cells and GLUT12 in ionocytes/ciliated cells. In addition to alveolar cells, SGLT1 transcripts were present in secretory cells. GLUT3 mRNA transcripts were expressed in a cell cluster that expressed monocarboxylate (MCT2) transporters. Such distributions likely underlie cell specific metabolic requirements to support proliferation, ion transport, mucous secretion, environment sensing and airway glucose homeostasis. These studies have also highlighted the role of glucose transporters in the movement of dehydroascorbic acid/vitamin C/myoinositol/urate which are factors important to the innate immune properties of the airways. Discrepancies remain between detection of mRNAs, protein and function of glucose transporters in the lungs. However, collation of the data from further scRNAseq studies may provide a better consensus and understanding, supported by qPCR, immunohistochemistry and functional experiments.

Diabetes Causes Significant Alterations in Pulmonary Glucose Transporter Expression

“…As the predominate insulin-sensitive GLUT in the body, we also sought to determine whether pulmonary GLUT4 trafficking could be stimulated ex vivo with acute insulin treatment (via 30 min insulin incubation of lung homogenates). Although GLUT4 has been detected in human trachea, bronchioles, and primary human bronchial epithelial cells [5,19], to our knowledge, no studies have described the specific insulin response as it relates to this major transporter in this tissue. The current study described the presence and activity of GLUT4 in adult mouse lungs (as opposed to in vitro studies or human samples) [9].…”

“…Other GLUTs, such as GLUT4, require activation by insulin to translocate from an intracellular vesicle to the cell surface in order to enable glucose diffusion into insulin-sensitive tissues. To the best of our knowledge, the protein expression of only a few GLUT isoforms have been reported in non-cancerous adult whole mammal lung (including rodents and humans) [5,19], although recent data have indicated that GLUT 1 and GLUT4 protein are also altered in the lung during SARS-CoV-2 infection in felines [20,21]. This study comprehensively evaluated both the gene and protein expression of the most predominant GLUT isoforms of Classes I and III in the lung of adult healthy mice in the same study.…”