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bioRxiv · 10.1101/2023.06.01.543344

A Novel Angiogenesis Role of GLP-1(32-36) to Rescue Diabetic Ischemic Lower Limbs via GLP-1R-Dependent Glycolysis

Zheng, C.·Zhang, Y.·Wang, S.·Zhou, Q.·Hu, Y.·Xie, Y.·Fang, W.·Yang, C.·Wang, Z.·Ye, S.·Wang, X.
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Abstract

Glucagon-like peptide 1 (GLP-1) improves angiogenesis, but the mechanism remains unclear. To address this question, we conducted a metabolomics analysis in bone marrow-derived endothelial progenitor cells (EPCs) isolated from T1DM mice treated with or without GLP-1(32-36) amide, an end-product of GLP-1. GLP-1(32-36) treatment recovered glycolysis. In addition, GLP-1(32-36) treatment rescued diabetic ischemic lower limbs and EPCs dysfunction by regulating PFKFB3-driven glycolytic flux capacity and mitochondrial dynamics. The effects of GLP-1(32-36) were abolished in mice lacking a functional GLP-1 receptor (Glp1r-/-), which could be partially rescued in EPCs transiently expressing GLP-1R. GLP-1(32-36) treatment activated the eNOS/cGMP/PKG pathway, increased glycolysis, and enhanced EPCs angiogenesis. Taken together, these findings suggest that GLP-1(32-36) could be used as a monotherapy or add-on therapy with existing treatments for DPAD. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=117 SRC="FIGDIR/small/543344v1_ufig1.gif" ALT="Figure 1"> View larger version (50K): org.highwire.dtl.DTLVardef@2559eorg.highwire.dtl.DTLVardef@1430faborg.highwire.dtl.DTLVardef@1b9b188org.highwire.dtl.DTLVardef@36809c_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Zheng, C., Zhang, Y., Wang, S., Zhou, Q., Hu, Y., Xie, Y., Fang, W., Yang, C., Wang, Z., Ye, S., Wang, X.. 2023-06-05. A Novel Angiogenesis Role of GLP-1(32-36) to Rescue Diabetic Ischemic Lower Limbs via GLP-1R-Dependent Glycolysis. https://doi.org/10.1101/2023.06.01.543344

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