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Insulin facilitates the hepatic clearance of plasma amyloid beta-peptide (1 40) by intracellular translocation of low-density lipoprotein receptor-related protein 1 (LRP-1) to the plasma membrane in hepatocytes.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Tamaki, Chihiro Ohtsuki, Sumio Terasaki, Tetsuya |
| Copyright Year | 2007 |
| Abstract | The hepatic clearance of amyloid beta-peptide (1-40) [Abeta(1-40)] from plasma, which is largely mediated by low-density lipoprotein receptor-related protein (LRP-1), is suggested to play a role in preventing Abeta(1-40) accumulation in the brain. Epidemiological investigations suggest a high incidence of cerebral Abeta deposition in insulin-resistant type II diabetes mellitus. The purpose of this study was to clarify the effect of insulin on the hepatic clearance of Abeta(1-40). LRP-1 expression on the hepatic plasma membrane was increased in a time-dependent manner by portal infusion of insulin and was 2.2-fold greater than that in nontreated controls after a 10-min infusion, whereas the expression in whole lysate was not affected by insulin treatment. The apparent hepatic uptake of [(125)I]Abeta(1-40) was also induced by insulin in a time-dependent manner. The increase in [(125)I]Abeta(1-40) uptake by insulin was concentration-dependent (EC(50) = 230 pM) and was completely abolished by receptor-associated protein (2 muM), an LRP-1 inhibitor. In conclusion, plasma insulin facilitates LRP-1 translocation to the hepatic plasma membrane from the intracellular pool, resulting in significant enhancement of hepatic Abeta(1-40) uptake from the circulating blood. The presently proposed mechanism would explain the epidemiological results demonstrating that type II diabetes mellitus is a risk factor of Alzheimer's disease. |
| File Format | PDF HTM / HTML |
| DOI | 10.1124/mol.107.036913 |
| PubMed reference number | 17609417 |
| Journal | Medline |
| Volume Number | 72 |
| Issue Number | 4 |
| Alternate Webpage(s) | http://molpharm.aspetjournals.org/content/molpharm/72/4/850.full.pdf |
| Alternate Webpage(s) | https://doi.org/10.1124/mol.107.036913 |
| Journal | Molecular pharmacology |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
