Article Publish Status: FREE
Abstract Title:

Brain insulin impairs amyloid-beta(1-40) clearance from the brain.

Abstract Source:

J Neurosci. 2004 Oct 27 ;24(43):9632-7. PMID: 15509750

Abstract Author(s):

Takeshi Shiiki, Sumio Ohtsuki, Atsushi Kurihara, Hideo Naganuma, Kenji Nishimura, Masanori Tachikawa, Ken-ichi Hosoya, Tetsuya Terasaki

Article Affiliation:

Drug Metabolism and Pharmacokinetics Research Laboratories, Sankyo Company, Shinagawa-ku, Tokyo 140-8710, Japan. [email protected]


Cerebral amyloid-beta peptide (Abeta) clearance plays a key role in determining the brain level of Abeta; however, its mechanism remains unclear. In this study, we investigated cerebral Abeta clearance across the blood-brain barrier (BBB) by using the Brain Efflux Index method. [125I]Abeta(1-40) was eliminated from rat brain to circulating blood with a half-life of 48.8 min and a half-saturation concentration of 8.15 nm. The Abeta(1-40) elimination rate was reduced by 30.5% in 23-month-old rats compared with 7-week-old rats. The intact form of Abeta(1-40) was detected in plasma after intracerebral administration, indicating the occurrence of efflux transport of intact Abeta(1-40). The Abeta(1-40) elimination rate was significantly inhibited by coadministration of 100 microg/ml insulin and 1 mm thiorphan by 44.6 and 34.0%, respectively. The level of intact [125I]Abeta(1-40) in the brain was increased by coadministration of insulin. Among insulin-degrading enzyme inhibitors, bacitracin inhibited the elimination rate, whereas N-ethylmaleimide and metal chelators had no effect. Receptor-associated protein, fucoidan, 3-bromo-5-t-butyl-4-hydroxy-benzylidenemalonitrile, anti-IGF-I receptor antibody, and l-tyrosine did not affect the Abeta(1-40) elimination rate, suggesting that the relevant receptors or transporters are not likely to be involved in the clearance. In conclusion, the present study has demonstrated the involvement of a proteolytic degradation process and an insulin-sensitive process in cerebral Abeta(1-40) clearance in the rat.

Study Type : Animal Study

Print Options

Key Research Topics

Sayer Ji
Founder of

Subscribe to our informative Newsletter & receive The Dark Side of Wheat Ebook

Our newsletter serves 500,000 with essential news, research & healthy tips, daily.

Download Now

The Dark Side of Wheat

This website is for information purposes only. By providing the information contained herein we are not diagnosing, treating, curing, mitigating, or preventing any type of disease or medical condition. Before beginning any type of natural, integrative or conventional treatment regimen, it is advisable to seek the advice of a licensed healthcare professional.

© Copyright 2008-2023, Journal Articles copyright of original owners, MeSH copyright NLM.