. Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature. 2005 Jul 21;436(7049):356-62. PubMed.


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  1. The elegant series of experiments by Yang et al. provide compelling evidence that increased serum retinol binding protein 4 is an important contributor to the pathogenesis of insulin resistance that is associated with a variety of genetic and environmental causes. This intriguing possibility has potential implications for Alzheimer disease (AD). Insulin resistance and related hyperinsulinemia increase the risk of AD, raising questions of whether and how abnormal levels of retinol binding protein 4 may factor into this risk (1). Interestingly, two papers have reported increased retinol binding protein 4 levels in the CSF of AD patients (2,3). In a recent review, Lane and Bailey present evidence for the role of retinol binding protein in regulation of retinoid signaling that may affect hippocampal long-term potentiation, neurogenesis, and β-amyloid plaque formation (4). As Yang et al. describe, it is well-known that retinol binding protein 4 complexes with and thereby regulates activity of transthyretin, a carrier protein thought to modulate Aβ transport from brain to periphery (5). These tantalizing relationships await further exploration and integration in a model of the pathway through which insulin resistance promotes AD pathogenesis.


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    . Immunodetection of protein composition in cerebral amyloid extracts in Alzheimer's disease: enrichment of retinol-binding protein. J Neurol Sci. 1987 Sep;80(2-3):221-8. PubMed.

    . Proteomic studies of potential cerebrospinal fluid protein markers for Alzheimer's disease. Brain Res Mol Brain Res. 2003 Oct 21;118(1-2):140-6. PubMed.

    . Role of retinoid signalling in the adult brain. Prog Neurobiol. 2005 Mar;75(4):275-93. PubMed.

    . Serum insulin-like growth factor I regulates brain amyloid-beta levels. Nat Med. 2002 Dec;8(12):1390-7. PubMed.

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