Carboxyl group-terminated polyamidoamine dendrimers bearing glucosides inhibit intestinal hexose transporter-mediated D-glucose uptake

Eur J Pharm Biopharm. 2010 Aug;75(3):366-74. doi: 10.1016/j.ejpb.2010.04.003. Epub 2010 Apr 24.


We are investigating non-absorbable polymeric conjugates bearing glucosides via a omega-amino triethylene glycol linker as oral anti-diabetic drugs that suppress an increase in the blood glucose level after meals through inhibition of Na(+)/glucose cotransporter (SGLT1). When the linker was bound to phloridzin, which is a SGLT1 inhibitor, to yield a precursor of the conjugate, the in vitro inhibitory effect on SGLT1-mediated d-glucose uptake was reduced to about one-tenth that of phloridzin. The inhibitory effect was recovered completely when the precursor was immobilized on the surface of poly(amidoamine) (PAMAM) dendrimers (generation: 3.0) by coupling with one-eighth or less of the terminal carboxyl groups. We considered that the phloridzin-derived glucose moiety on the dendrimer surface was prerequisite for SGLT1 inhibition but that the aglycon part was not always required for the inhibition. Commercially used arbutin, a SGLT1 substrate, was substituted for phloridzin whose aglycon is composed of toxic phloretin. The in vitro inhibitory effect of arbutin was about one-thirtieth that of intact phloridzin; however, the inhibitory effect of the PAMAM dendrimer-arbutin conjugates was as strong as that of the PAMAM dendrimer-phloridzin conjugates. Rat experiments further showed that the PAMAM dendrimer-arbutin conjugates significantly suppressed d-glucose-induced hyperglycemic effects. The dendritic conjugate bearing arbutin appears to be a good candidate as an oral anti-diabetic drug.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dendrimers / chemistry*
  • Glucose / metabolism*
  • Glucosides / chemistry*
  • Intestinal Mucosa / metabolism*
  • Magnetic Resonance Spectroscopy
  • Male
  • Monosaccharide Transport Proteins / antagonists & inhibitors*
  • Monosaccharide Transport Proteins / physiology
  • Rats
  • Rats, Wistar
  • Spectrometry, Mass, Fast Atom Bombardment


  • Dendrimers
  • Glucosides
  • Monosaccharide Transport Proteins
  • PAMAM Starburst
  • Glucose