HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Online-Only Appendix All Versions of this Article: db07-0394v1 56/8/2028    most recent Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content PubMed PubMed Citation Social Bookmarking                What's this?

Soluble Insulin Receptor Ectodomain Is Elevated in the Plasma of Patients With Diabetes

Address correspondence and reprint requests to Yousuke Ebina, MD, PhD, Division of Molecular Genetics, Institute for Enzyme Research, The University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan. E-mail: ebina{at}ier.tokushima-u.ac.jp

Abbreviations: ELISA, enzyme-linked immunosorbent assay; FPG, fasting plasma glucose; hIR, human insulin receptor; IL, interleukin; IR, insulin receptor; IRI, immunoreactive insulin; MMP, membrane-tethered zinc metalloproteinases; PKC, protein kinase C; STZ, streptozotocin; TNF, tumor necrosis factor; WGA, wheat-germ agglutinin

OBJECTIVE—Insulin binds to the -subunit of the insulin receptor (IR) and subsequently exerts its effects in the cells. The soluble ectodomains of several receptors have been found to circulate in the plasma. Therefore, we hypothesized that soluble human insulin receptor (hIR) ectodomain (-subunit and a part of ß-subunit) may exist in the plasma of diabetic patients.

RESEARCH DESIGN AND METHODS—We identified soluble hIR ectodomain in human plasma by a two-step purification followed by immunoblotting and gel-filtration chromatography. Furthermore, we established an hIR-specific enzyme-linked immunosorbent assay and measured the plasma IR levels in patients with diabetes. We also investigated this phenomenon in streptozotocin-induced diabetic hIR transgenic mice.

RESULTS—Soluble hIR, but not intact hIRß or whole hIR, exists in human plasma. The plasma IR levels were significantly higher in type 1 (2.00 ± 0.60 ng/ml; n = 53) and type 2 (2.26 ± 0.80; n = 473) diabetic patients than in control subjects (1.59 ± 0.40 ng/ml; n = 123 (P < 0.001 vs. control). Plasma IR level was positively correlated with blood glucose level, and 10–20% of the insulin in plasma bound to hIR. In the in vivo experiments using diabetic hIR transgenic mice, hyperglycemia was confirmed to increase the plasma hIR level and the half-life estimated to be 6 h.

CONCLUSIONS—We propose that the increased soluble IR ectodomain level appears to be a more rapid glycemic marker than A1C or glycoalbumin.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?