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首页> 外文期刊>Advanced Functional Materials >Liver-Target and Glucose-Responsive Polymersomes toward Mimicking Endogenous Insulin Secretion with Improved Hepatic Glucose Utilization
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Liver-Target and Glucose-Responsive Polymersomes toward Mimicking Endogenous Insulin Secretion with Improved Hepatic Glucose Utilization

机译：肝靶和葡萄糖反应性聚合物囊泡通过改善肝脏葡萄糖利用来模仿内源性胰岛素分泌

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摘要

Oral insulin therapy that targets the liver and further mimics glucose-responsive secretion holds promise for correcting defects in glucose metabolism caused by peripheral delivery. This work describes the construction of polymersomes (Pep-PMS), which are composed of glucose-responsive polymers decorated with peptides that readily bind to the ganglioside-monosialic acid (GM1) receptor in the intestinal epithelium. Pep-PMS are efficiently transported across the intestinal epithelium through GM1-mediated transcytosis, leading to their abundant accumulation in the liver. Moreover, Pep-PMS can efficiently encapsulate insulin in euglycemia and release them in hyperglycemia. Under hyperglycemic conditions, the Pep-PMS dissociate to release the encapsulated insulin in response to glucose oxidase (GOx)-induced H2O2. Surprisingly, the postprandial blood glucose levels of diabetic rats treated with Pep-PMS can be maintained even after being challenged by glucose administration. Hepatic glucose uptake and glycogen production are also elevated after treating diabetic rats with Pep-PMS, which is similar to glucose utilization in normal rats. Oral delivery systems that target the liver and serve as a reservoir for glucose-responsive insulin secretion may improve the therapeutic effect in people with diabetes.
机译：靶向肝脏并进一步模拟葡萄糖反应性分泌的口服胰岛素疗法有望纠正由外周递送引起的葡萄糖代谢缺陷。这项工作描述了聚合物囊泡（Pep-PMS）的构建，该聚合物囊泡由葡萄糖响应性聚合物组成，该聚合物修饰有易于结合肠上皮神经节苷脂-单唾液酸（GM1）受体的肽。 Pep-PMS通过GM1介导的胞吞作用有效地穿过肠上皮运输，从而使其在肝脏中大量积累。而且，Pep-PMS可以有效地将胰岛素封装在正常血糖中，并在高血糖症中将其释放。在高血糖情况下，Pep-PMS会解离以响应葡萄糖氧化酶（GOx）诱导的H2O2释放封装的胰岛素。出人意料的是，即使受到葡萄糖挑战，仍可维持用Pep-PMS治疗的糖尿病大鼠的餐后血糖水平。用Pep-PMS治疗糖尿病大鼠后，肝葡萄糖摄取和糖原产生也增加，这与正常大鼠中的葡萄糖利用相似。以肝脏为目标的口服递送系统，可作为葡萄糖反应性胰岛素分泌的储存库，可改善糖尿病患者的治疗效果。

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