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Angiogenesis is the formation of new blood vessels from preexisting vasculature, an essential process during development and tumor growth. Endoglin is a TGF-β co-receptor expressed predominantly in proliferating endothelial cells required for angiogenesis. Recently, our lab discovered an unexpected novel cross-talk between insulin and TGF-β signaling pathways. The purpose of this study was to examine the role of endoglin in insulin-mediated Smad signaling. Immunofluorescence and biochemical methods were used to assess cellular changes in Smad1/5/8 activation (pro-angiogenic). Preliminary data indicates that endoglin expression is required for insulin induced Smad1/5/8 activation. Given that type 2 diabetic patients are susceptible to a number of vascular-related conditions and malignancies, our results reveal new pathophysiologic implications for Smad1/5/8 signaling through hyperinsulinemia during pre-diabetic and diabetic disease progression.