Impact of Delta SARS-CoV-2 Infection on Glucose Metabolism: Insights on Host Metabolism and Virus Crosstalk in a Feline Model

Abstract

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes enhanced mortality in people with metabolic and cardiovascular diseases. Other highly infectious RNA viruses have demonstrated dependence on glucose transport and utilization, so we hypothesized that SARS-CoV-2 infection could lead to alterations in cellular and whole-body glucose metabolism. Twenty-four healthy domestic cats were intratracheally inoculated with B.1.617.2 (delta) SARS-CoV-2 and samples were collected at 4- and 12-days post-inoculation (dpi). Blood glucose and circulating cortisol concentrations were elevated at 4 and 12 dpi. Serum insulin concentration was statistically significantly decreased, while angiotensin 2 concentration was elevated at 12 dpi. SARS-CoV-2 RNA was detected in the pancreas and skeletal muscle at low levels; however, no change in the number of insulin-producing cells or proinflammatory cytokines was observed in the pancreas of infected cats through 12 dpi. SARS-CoV-2 infection statistically significantly increased GLUT protein expression in both the heart and lungs, correlating with increased AMPK expression. In brief, SARS-CoV-2 increased blood glucose concentration and cardio-pulmonary GLUT expression through an AMPK-dependent mechanism, without affecting the pancreas, suggesting that SARS-CoV-2 induces the reprogramming of host glucose metabolism. A better understanding of host cell metabolism and virus crosstalk could lead to the discovery of novel metabolic therapeutic targets for patients affected by COVID-19.

Diabetes Causes Significant Alterations in Pulmonary Glucose Transporter Expression

“…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.…”