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

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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.