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A compound that produces identical protective effects whether administered systemically or topically to the target tissue suggests both a circulating effector mechanism and a local tissue-level mechanism, consistent with the dual NO-VEGF angiogenic pathway described above

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Discordance Between Endocrine and Paracrine/Autocrine IGF-I An important example of metabolic and mitogenic consequences of an unbalanced endocrine versus autocrine/paracrine insulin-GH-IGF-axis comes from observations in children and adolescents with type 1 diabetes (Figure 5)