| Quantitative Measurement of Full-Length and C-Terminal Proteolyzed RBP4 in Serum of Normal and Insulin-Resistant Humans using a Novel Mass Spectrometry Immunoassay. | |
| | |
MedLine Citation:
|
PMID: 22253430 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
Serum retinol-binding protein 4 (RBP4) levels are increased in insulin-resistant humans and correlate with severity of insulin resistance in metabolic syndrome. Quantitative Western blotting (qWestern) has been the most accurate method for serum RBP4 measurements, but qWestern is technically complex and labor intensive. The lack of a reliable, high-throughput method for RBP4 measurements has resulted in variability in findings in insulin-resistant humans. Many commonly used ELISAs have limited dynamic range. Neither the current ELISAs nor qWestern distinguish among full-length and carboxyl terminus proteolyzed forms of circulating RBP4 that are altered in different medical conditions. Here, we report the development of a novel quantitative mass spectrometry immunoaffinity assay (qMSIA) to measure full-length and proteolyzed forms of RBP4. qMSIA and qWestern of RBP4 were performed in identical serum aliquots from insulin-sensitive/normoglycemic or insulin-resistant humans with impaired glucose tolerance or type 2 diabetes. Total RBP4 qMSIA measurements were highly similar to qWestern and correlated equally well with clinical severity of insulin resistance (assessed by clamp glucose disposal rate, r = -0.74), hemoglobin A1c (r = 0.63), triglyceride/high-density lipoprotein (r = 0.55), waist/hip (r = 0.61), and systolic blood pressure (r = 0.53, all P < 0.001). Proteolyzed forms of RBP4 accounted for up to 50% of total RBP4 in insulin-resistant subjects, and des(Leu)-RBP4 (cleavage of last leucine) correlated highly with insulin resistance (assessed by glucose disposal rate, r = -0.69). In multiple regression analysis, insulin resistance but not glomerular filtration rate was the strongest, independent predictor of serum RBP4 levels. Thus, qMSIA provides a novel tool for accurately measuring serum RBP4 levels as a biomarker for severity of insulin resistance and risk for type 2 diabetes and metabolic syndrome. |
| | |
Authors:
|
Qin Yang; Iratxe Eskurza; Urban A Kiernan; David A Phillips; Matthias Blüher; Timothy E Graham; Barbara B Kahn |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2012-1-17 |
Journal Detail:
|
Title: Endocrinology Volume: - ISSN: 1945-7170 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
|
Created Date: 2012-1-18 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0375040 Medline TA: Endocrinology Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, (Q.Y., I.E., T.E.M., B.B.K.) Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215; Intrinsic Bioprobes, Inc./Thermo Fisher Scientific (U.A.K., D.A.P.), Tempe, Arizona 85284; and Department of Medicine (M.B.), University of Leipzig Medical Center, Leipzig, 4109, Germany. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Reduced Hippocampal Brain-Derived Neurotrophic Factor (BDNF) in Neonatal Rats after Prenatal Exposur...
Next Document: Thyroid Hormone Receptors Control Developmental Maturation of the Middle Ear and the Size of the Oss...