BCG Vaccinations Upregulate Myc, a Central Switch for Improved Glucose Metabolism in Diabetes
| Autor: | Hiroyuki Takahashi, Denise L. Faustman, Gabriella F. Shpilsky, Jessica C. Graham, Ryan C. Keefe, Louisa Moore, Yaerin Song, Trevor G. Luck, Lisa Tran, Willem M. Kühtreiber, Sarah M. Sinton |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Blood sugar 02 engineering and technology Article 03 medical and health sciences Downregulation and upregulation Diabetes mellitus medicine lcsh:Science Transcriptomics Transcription factor PI3K/AKT/mTOR pathway Multidisciplinary Glutaminolysis business.industry Glucose transporter Diabetology 021001 nanoscience & nanotechnology medicine.disease 030104 developmental biology Anaerobic glycolysis Immune System Cancer research lcsh:Q 0210 nano-technology business |
| Zdroj: | iScience iScience, Vol 23, Iss 5, Pp-(2020) |
| ISSN: | 2589-0042 |
| Popis: | Summary Myc has emerged as a pivotal transcription factor for four metabolic pathways: aerobic glycolysis, glutaminolysis, polyamine synthesis, and HIF-1α/mTOR. Each of these pathways accelerates the utilization of sugar. The BCG vaccine, a derivative of Mycobacteria-bovis, has been shown to trigger a long-term correction of blood sugar levels to near normal in type 1 diabetics (T1D). Here we reveal the underlying mechanisms behind this beneficial microbe-host interaction. We show that baseline glucose transport is deficient in T1D monocytes but is improved by BCG in vitro and in vivo. We then show, using RNAseq in monocytes and CD4 T cells, that BCG treatment over 56 weeks in humans is associated with upregulation of Myc and activation of nearly two dozen Myc-target genes underlying the four metabolic pathways. This is the first documentation of BCG induction of Myc and its association with systemic blood sugar control in a chronic disease like diabetes. Graphical Abstract Highlights • T1D has insufficient aerobic glycolysis; this causes insufficient sugar utilization • BCG vaccine lowers blood sugar levels in T1D by augmenting aerobic glycolysis • BCG-induced shift to aerobic glycolysis is associated with Myc activation • Host-microbe BCG interactions through Myc activate sugar-regulating genes in T1D Immune System; Diabetology; Transcriptomics |
| Databáze: | OpenAIRE |
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