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      Insulin-like growth factor (IGF)-I and IGF binding proteins axis in diabetes mellitus

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          Abstract

          Increasing evidence suggests an important role of the insulin-like growth factor (IGF)-IGF binding protein (IGFBP) axis in the maintenance of normal glucose and lipid metabolism. Significant changes occur in the local IGF-I-IGFBPs environment in response to the diabetic milieu. A significant reduction of serum IGF-I levels was observed in patients with type 1 diabetes mellitus (T1DM). Inversely, considerably increased serum levels of IGF-I and IGFBP-3 levels were detected in individuals with glucose intolerance including T2DM. Recently, several prospective studies indicated that baseline levels of IGF-I and IGFBPs are associated with the development of diabetes. These findings suggest that disturbances in insulin and IGF-I-IGFBP axis can affect the development of glucose intolerance including diabetes.

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          Insulin-like growth factors and their binding proteins: biological actions.

          D Clemmons, J Jones (1995)
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            Insulin-like growth factor I receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity.

            A Ullrich, A. Gray, A W Tam … (1986)
            To identify structural characteristics of the closely related cell surface receptors for insulin and IGF-I that define their distinct physiological roles, we determined the complete primary structure of the human IGF-I receptor from cloned cDNA. The deduced sequence predicts a 1367 amino acid receptor precursor, including a 30-residue signal peptide, which is removed during translocation of the nascent polypeptide chain. The 1337 residue, unmodified proreceptor polypeptide has a predicted Mr of 151,869, which compares with the 180,000 Mr IGF-I receptor precursor. In analogy with the 152,784 Mr insulin receptor precursor, cleavage of the Arg-Lys-Arg-Arg sequence at position 707 of the IGF-I receptor precursor will generate alpha (80,423 Mr) and beta (70,866 Mr) subunits, which compare with approximately 135,000 Mr (alpha) and 90,000 Mr (beta) fully glycosylated subunits.
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              Circulating concentrations of insulin-like growth factor-I and development of glucose intolerance: a prospective observational study.

              Manjinder S. Sandhu, Adrian H Heald, J. Gibson … (2002)
              Results of experimental and clinical studies suggest that insulin-like growth factor-I (IGF-I) and IGF binding protein-1 (IGFBP-1) could be important determinants of glucose homoeostasis. However, experimental models might also reflect compensatory and adaptive metabolic processes. We therefore prospectively examined the associations between circulating concentrations of IGF-I and IGFBP-1 and development of glucose tolerance. Participants in this cohort study were a random sample of 615 normoglycaemic men and women aged 45-65 years. Participants underwent oral glucose tolerance testing based on WHO definitions and criteria in 1990-92 and 1994-96. At the baseline visit, we measured serum concentrations of IGF-I and IGFBP-1, and assessed the relation between these peptides and subsequent glucose intolerance. At 4.5 years of follow-up, 51 (8%) of 615 participants developed impaired glucose tolerance or type-2 diabetes. After adjustment for correlates of IGF-I and risk factors for glucose intolerance, the odds ratio for risk of impaired glucose tolerance or type-2 diabetes for participants with IGF-I concentrations above the median (> or = 152 microg/L) compared with those with concentrations below the median (<152 microg/L) was 0.50 (0.26-0.95). Consistent with this finding, IGF-I also showed a significant inverse association with subsequent 2-h glucose concentrations, which was independent of correlates of IGF-I and risk factors for glucose tolerance (p for linear trend=0.026). We also found that this inverse association was independently modified by IGFBP-1 (p for interaction=0.011). These data show that circulating IGF-I and its interaction with IGFBP-1 could be important determinants of glucose homoeostasis and provide further evidence for the possible protective role of IGF-I against development of glucose intolerance.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Ann Pediatr Endocrinol Metab
                Journal ID (iso-abbrev): Ann Pediatr Endocrinol Metab
                Journal ID (publisher-id): APEM
                Title: Annals of Pediatric Endocrinology & Metabolism
                Publisher: The Korean Society of Pediatric Endocrinology
                ISSN (Print): 2287-1012
                ISSN (Electronic): 2287-1292
                Publication date (Print): June 2015
                Publication date (Electronic): 30 June 2015
                Volume: 20
                Issue: 2
                Pages: 69-73
                Affiliations
                Department of Pediatrics, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Institute of Chonbuk National University Hospital, Jeonju, Korea.
                Author notes
                Address for correspondence: Dae-Yeol Lee, MD. Department of Pediatrics, Chonbuk National University Children's Hospital, 20 Geonji-ro, Deokjin-gu, Jeonju 561-712, Korea. Tel: +82-63-250-1469, Fax: +82-63-250-1464, leedy@ 123456jbnu.ac.kr
                Article
                DOI: 10.6065/apem.2015.20.2.69
                PMC ID: 4504992
                PubMed ID: 26191509
                SO-VID: 64effb37-031f-4efc-854f-923c87b0b582
                Copyright © © 2015 Annals of Pediatric Endocrinology & Metabolism
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 23 June 2015
                Date accepted : 24 June 2015
                Categories
                Subject: Review Article

                Keywords: diabetes mellitus,insulin-like growth factor i,insulin-like growth factor binding protein 1,insulin-like growth factor binding protein 3,lipid metabolism
                Data availability:
                Keywords: diabetes mellitus, insulin-like growth factor i, insulin-like growth factor binding protein 1, insulin-like growth factor binding protein 3, lipid metabolism

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