| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,§1
* Institute of Pharmacological Sciences, University of Milano, Milan, Italy;
Department of Internal Medicine, Geriatrics and Gerontology Clinic,
Institute of Pharmacology University of Pavia, Pavia, Italy; and
§ IRCCS ‘Centro S. Giovanni di Dio - FBF’ Brescia, Brescia, Italy
1Correspondence: Institute of Pharmacology, University of Pavia, Viale Taramelli 14, 27100 Pavia, Italy. E-mail: racchi{at}unipv.it
Several lines of biochemical evidence correlate the presence of energy metabolic defects with the functional alterations associated with brain aging and with the pathogenesis of neurodegenerative disorders such as Alzheimer’s disease. Within this context we tested the ability of insulin to regulate the amyloid precursor protein (APP) processing in SH-SY5Y neuroblastoma cells. Our findings show that insulin promotes APP metabolism by a glucose-independent mechanism. We demonstrate a novel intracellular pathway that increases the rate of secretion of soluble APP through the activity of phosphatidyl-inositol 3 kinase (PI3-K). This pathway, downstream of insulin receptor tyrosine kinase activity, does not involve either the activation of protein kinase C or the mitogen-activated protein kinase (MAP-K) pathway. Because of the physiological role of PI3-K in the translocation of glucose transporter-containing vesicles, we speculate that PI3-K involvement in APP metabolism may act at the level of vesicular trafficking.—Solano, D. C., Sironi, M., Bonfini, C., Solerte, S. B., Govoni, S., Racchi, M. Insulin regulates soluble amyloid precursor protein release via phosphatidyl inositol 3 kinase-dependent pathway.
Key Words: signal transduction • PI3 kinase • Alzheimer’s disease • 
secretase
This article has been cited by other articles:
|
|
 |
|
  W. A. Banks, S. Dohgu, J. L. Lynch, M. A. Fleegal-DeMotta, M. A. Erickson, R. Nakaoke, and T. Q. Vo Nitric Oxide Isoenzymes Regulate Lipopolysaccharide-Enhanced Insulin Transport across the Blood-Brain Barrier Endocrinology, April 1, 2008; 149(4): 1514 - 1523. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-D. Chen, S. Podvin, E. Gillespie, S. E. Leeman, and C. R. Abraham Insulin stimulates the cleavage and release of the extracellular domain of Klotho by ADAM10 and ADAM17 PNAS, December 11, 2007; 104(50): 19796 - 19801. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z.-g. Li, W. Zhang, and A. A.F. Sima Alzheimer-Like Changes in Rat Models of Spontaneous Diabetes Diabetes, July 1, 2007; 56(7): 1817 - 1824. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Adlerz, S. Holback, G. Multhaup, and K. Iverfeldt IGF-1-induced Processing of the Amyloid Precursor Protein Family Is Mediated by Different Signaling Pathways J. Biol. Chem., April 6, 2007; 282(14): 10203 - 10209. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. I. Duarte, M. S. Santos, R. Seica, and C. R. Oliveira Oxidative Stress Affects Synaptosomal {gamma}-Aminobutyric Acid and Glutamate Transport in Diabetic Rats: The Role of Insulin Diabetes, August 1, 2004; 53(8): 2110 - 2116. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Peila, B. L. Rodriguez, L. R. White, and L. J. Launer Fasting insulin and incident dementia in an elderly population of Japanese-American men Neurology, July 27, 2004; 63(2): 228 - 233. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Schubert, D. P. Brazil, D. J. Burks, J. A. Kushner, J. Ye, C. L. Flint, J. Farhang-Fallah, P. Dikkes, X. M. Warot, C. Rio, et al. Insulin Receptor Substrate-2 Deficiency Impairs Brain Growth and Promotes Tau Phosphorylation J. Neurosci., August 6, 2003; 23(18): 7084 - 7092. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D Liolitsa, J Powell, and S Lovestone Genetic variability in the insulin signalling pathway may contribute to the risk of late onset Alzheimer's disease J. Neurol. Neurosurg. Psychiatry, September 1, 2002; 73(3): 261 - 266. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.-P. Xu, D. Zoukhri, J. D. Zieske, D. A. Dartt, C. Sergheraert, E. Loing, and F.-S. X. Yu A role for MAP kinase in regulating ectodomain shedding of APLP2 in corneal epithelial cells Am J Physiol Cell Physiol, August 1, 2001; 281(2): C603 - C614. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Gasparini, G. K. Gouras, R. Wang, R. S. Gross, M. F. Beal, P. Greengard, and H. Xu Stimulation of {beta}-Amyloid Precursor Protein Trafficking by Insulin Reduces Intraneuronal {beta}-Amyloid and Requires Mitogen-Activated Protein Kinase Signaling J. Neurosci., April 15, 2001; 21(8): 2561 - 2570. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
