Manipulation of gastrointestinal functions by polymeric conjugates bearing glucosides, oral anti-diabetic drugs

人类饮食中的碳水化合物被胃肠道中的消化酶降解。由此产生的单糖，如葡萄糖，通过内流的己糖转运体从小肠吸收，主要是钠依赖的钠/葡萄糖共转运体(SGLT1)。碳水化合物还可诱导肠道L细胞分泌胰升糖素样肽1。胰岛素分泌随后被GLP-1增强，因为这种多肽刺激胰腺中的SS细胞。合成了含有糖苷的聚合物结合物，并检测了它们对SGLT1抑制和诱导GLP-1分泌的能力。我们成功地证明了含有熊果苷的端羧基聚酰胺胺树枝状大分子是一种潜在的具有上述功能的口服降糖药物。

Carbohydrates in the human diet are hydrolyzed by digestive enzymes in the gastrointestinal tract. The resulting monosaccharides, such as glucose, are absorbed from the small intestine via influx hexose transporters, mainly sodium-dependent Na+/glucose cotransporters(SGLT1). Carbohydrates also induce the secretion of glucagon-like peptide 1(GLP-1) from intestinal L cells. Insulin secretion is subsequently enhanced by GLP-1 because this peptide stimulates ss cells in pancreas. Polymeric conjugates bearing glucosides were synthesized and their abilities for SGLT1 inhibition and induction of GLP-1 secretion were examined. We successfully proved that carboxyl group-terminated polyamidoamine dendrimers bearing arbutin was a potential candidate as oral anti-diabetic drugs having above-mentioned abilities.