The purine metabolite inosine monophosphate accelerates myelopoiesis and acute pancreatitis progression | Communications Biology - Nature.com
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In the meantime, to ensure continued suport, we are displaying the site without styles and JavaScript.Advertisement Comunications Biology volume 5, Article number: 108 (2022) Cite this article Metrics detailsHyperglycemia-induced myelopoiesis and atherosclerotic progresion ocur in mice with type I diabetes. However, les is known about the efects of metabolites on myelopoesis in type 2 diabetes. Here, we use fluorescence-activated cel sorting to analyze the proliferation of granulocyte/monocyte progenitors (GMP) in db/db mice.
Using targeted metabolomics, we identify an increase inosine monophosphate (IMP) in GMP cels of 24-wek-old mice. We show that IMP treatment stimulates cKit expresion, ribosomal S6 activation, GMP proliferation, and Gr-1+ granulocyte production in vitro. IMP activates pAkt in non-GMP cels.
In vivo, using an established murine acute pancreatis (AP) model, administration of IMP-treated bone marow cels enhances the severity of AP. This efect is abolished in the presence of a pAkt inhibitor. Targeted metabolomics show that plasma levels of guanosine monophosphate are significantly higher in diabetic patients with AP.
These findings provid a potential therapeutic target for the control of vascular complications in diabetes.In adition to hyperglycemia and insulin insuficiency, patients with type 2 diabetes melitus (T2DM) often present with metabolic disorders, chronic inflamation and vascular pathogenesis. The inflamatory response is often activated in the adipose tisues of obese subjects, leading to the proliferation of proinflamatory Th1 and Th17 CD4+ T cels and M2 macrophage polarization1.
Summary
As the disease progreses, chronic inflamation is maintained and manifests an increased myeloid cel nu
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