| Carboxyl group-terminated polyamidoamine dendrimers bearing glucosides inhibit intestinal hexose transporter-mediated D-glucose uptake. | |
| | |
MedLine Citation:
|
PMID: 20399853 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
Shinji Sakuma; Yumi Teraoka; Tomokazu Sagawa; Yoshie Masaoka; Makoto Kataoka; Shinji Yamashita; Yoshiyuki Shirasaka; Ikumi Tamai; Yusuke Ikumi; Toshiyuki Kida; Mitsuru Akashi |
Related Documents
:
|
5820643 - Structural requirements for active intestinal transport. spatial and bonding requiremen... 3521743 - Fibroblast growth factor induces a transient net k+ influx carried by the bumetanide-se... 20558843 - Chronic placental ischemia alters amniotic fluid milieu and results in impaired glucose... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-04-24 |
Journal Detail:
|
Title: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft für Pharmazeutische Verfahrenstechnik e.V Volume: 75 ISSN: 1873-3441 ISO Abbreviation: Eur J Pharm Biopharm Publication Date: 2010 Aug |
Date Detail:
|
Created Date: 2010-07-12 Completed Date: 2010-11-26 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 9109778 Medline TA: Eur J Pharm Biopharm Country: Netherlands |
Other Details:
|
Languages: eng Pagination: 366-74 Citation Subset: IM |
Affiliation:
|
Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, Japan. sakuma@pharm.setsunan.ac.jp |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Dendrimers / chemistry* Glucose / metabolism* Glucosides / chemistry* Intestines / metabolism* Magnetic Resonance Spectroscopy Male Monosaccharide Transport Proteins / antagonists & inhibitors*, physiology Rats Rats, Wistar Spectrometry, Mass, Fast Atom Bombardment |
| Chemical | |
Reg. No./Substance:
|
0/Dendrimers; 0/Glucosides; 0/Monosaccharide Transport Proteins; 0/PAMAM Starburst; 50-99-7/Glucose |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Dihydroorotate dehydrogenase is required for N-(4-hydroxyphenyl)retinamide-induced reactive oxygen s...
Next Document: Long term genistein treatment of MCF-7 cells decreases acetylated histone 3 expression and alters gr...