INGAP-PP 对β细胞质量和功能的影响与其对胰岛血管生成和 VEGFA 产生的积极作用有关。
INGAP-PP effects on β-cell mass and function are related to its positive effect on islet angiogenesis and VEGFA production.
机构信息
CENEXA, Centro de Endocrinología Experimental y Aplicada (UNLP-CONICET La Plata), Facultad de Ciencias Médicas UNLP, 60 y 120 (s/n) 4to piso, 1900 La Plata, Argentina.
CENEXA, Centro de Endocrinología Experimental y Aplicada (UNLP-CONICET La Plata), Facultad de Ciencias Médicas UNLP, 60 y 120 (s/n) 4to piso, 1900 La Plata, Argentina.
出版信息
Mol Cell Endocrinol. 2018 Jul 15;470:269-280. doi: 10.1016/j.mce.2017.11.009. Epub 2017 Nov 13.
Our aim was to determine whether islet angiogenesis and VEGFA production/release participate in the mechanism by which INGAP-PP enhances β-cell function and mass. We used two models: a) in vivo (normal rats injected with INGAP-PP for 10 days) and b) in vitro (normal islets cultured for 4 days with INGAP-PP, VEGFA, Rapamycin, and the specific VEGF-Receptor inhibitor, SU5416). INGAP-PP administration enhanced insulin secretion, β-cell mass, islet vascularization, and angiogenesis without affecting glucose homeostasis. Normal islets cultured with INGAP-PP and VEGFA increased insulin and VEGFA secretion while apoptosis decreased. INGAP-PP-induced effects were prevented by both Rapamycin and SU5416. INGAP-PP effects on β-cell mass and function were significantly associated with a positive effect on islet angiogenesis and VEGFA production/release. VEGF-A possibly potentiates INGAP-PP effect through mTORC pathway.
我们的目的是确定胰岛血管生成和 VEGFA 的产生/释放是否参与 INGAP-PP 增强 β 细胞功能和质量的机制。我们使用了两种模型：a）体内（正常大鼠注射 INGAP-PP 10 天）和 b）体外（正常胰岛培养 4 天与 INGAP-PP、VEGFA、雷帕霉素和特异性 VEGF 受体抑制剂 SU5416）。INGAP-PP 给药增强了胰岛素分泌、β 细胞质量、胰岛血管生成和血管生成，而不影响葡萄糖稳态。与对照组相比，用 INGAP-PP 和 VEGFA 培养的正常胰岛增加了胰岛素和 VEGFA 的分泌，同时减少了细胞凋亡。雷帕霉素和 SU5416 均可阻止 INGAP-PP 诱导的作用。INGAP-PP 对 β 细胞质量和功能的影响与对胰岛血管生成和 VEGFA 产生/释放的积极影响显著相关。VEGF-A 可能通过 mTORC 通路增强 INGAP-PP 的作用。
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