Proinsulin C-peptide prevents hyperglycemia-induced vascular leakage and metastasis of melanoma cells in the lungs of diabetic mice

What is it about?

C-peptide has a beneficial effect against diabetic complications, but its role in hyperglycemia-induced metastasis is unknown. _x000D_ Thus, we investigated hyperglycemia-mediated pulmonary vascular leakage and metastasis and C-peptide inhibition of these molecular events using human pulmonary microvascular endothelial cells and streptozotocin-induced diabetic mice. _x000D_ In this study, we present three key findings: (i) hyperglycemia stimulates cancer metastasis, (ii) this stimulation can be prevented by C-peptide supplementation, and (iii) the important role of transglutaminase 2 in VEGF-stimulated pulmonary vascular leakage and lung metastasis. Thus, we propose that transglutaminase 2 is the key enzyme for hyperglycemia-induced lung metastasis and that C-peptide is a potential therapeutic candidate for treating diabetic metastasis.

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