This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map 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 Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by O’Connell, T. Articles by Clemmons, D. R. Search for Related Content PubMed PubMed Citation Articles by O’Connell, T. Articles by Clemmons, D. R.

IGF-I/IGF-Binding Protein-3 Combination Improves Insulin Resistance By GH-Dependent and Independent Mechanisms

Department of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599

Abstract

IGF-I has been shown to enhance insulin sensitivity in patients with type I and type II diabetes. IGF-I suppresses GH, and this raises the question of whether its ability to enhance insulin sensitivity is mediated solely through a reduction in GH’s antiinsulin actions. This study was conducted to determine whether administration of a GH receptor antagonist to patients with acromegaly and insulin resistance would result in improvement in insulin sensitivity and whether IGF-I had any additional insulin-sensitizing effects over and above those induced by its ability to suppress GH secretion. Five patients with active acromegaly were treated for 2 wk with a GH receptor antagonist. The GH receptor antagonist was effective, as IGF-I fell 65%, and mean GH values rose 42%. Mean fasting insulin fell from 39 ± 6 to 30 ± 7 µU/ml, and this was accompanied by a 9% decrease in fasting glucose. After treatment the insulin sensitivity index was 2.7 ± 1.0 x 10^-4/min·µU/ml compared with a baseline value of 1.65 ± 0.8 x 10^-4/min·µU/ml (P < 0.015). Subsequently, the subjects were treated with the receptor antagonist plus IGF-I/IGF-binding protein-3 given by sc injection (1 mg/kg daily). After 2 wk of the combined treatment, fasting insulin fell from 49 ± 9 to 29 ± 7 µU/ml, and fasting glucose fell by 14%. The insulin sensitivity index improved to 4.34 ± 1.3 x 10^-4/min·µU/ml, which was significantly greater than the value obtained after treatment with the GH antagonist alone. Although only a limited number of subjects were studied, the results strongly suggest that IGF-I has insulin-sensitizing actions that are independent of its ability to suppress GH secretion. These findings necessitate further studies into the non-GH-related mechanism by which IGF-I enhances insulin sensitivity.

This article has been cited by other articles:

				N. Moller and J. O. L. Jorgensen Effects of Growth Hormone on Glucose, Lipid, and Protein Metabolism in Human Subjects Endocr. Rev., April 1, 2009; 30(2): 152 - 177. [Abstract] [Full Text] [PDF]

				R. H. Muzumdar, X. Ma, S. Fishman, X. Yang, G. Atzmon, P. Vuguin, F. H. Einstein, D. Hwang, P. Cohen, and N. Barzilai Central and Opposing Effects of IGF-I and IGF-Binding Protein-3 on Systemic Insulin Action. Diabetes, October 1, 2006; 55(10): 2788 - 2796. [Abstract] [Full Text] [PDF]

				E. Rico-Bautista, C. J. Greenhalgh, P. Tollet-Egnell, D. J. Hilton, W. S. Alexander, G. Norstedt, and A. Flores-Morales Suppressor of Cytokine Signaling-2 Deficiency Induces Molecular and Metabolic Changes that Partially Overlap with Growth Hormone-Dependent Effects Mol. Endocrinol., March 1, 2005; 19(3): 781 - 793. [Abstract] [Full Text] [PDF]

				T. Saukkonen, R. Amin, R. M. Williams, C. Fox, K. C. Yuen, M. A. White, A. M. Umpleby, C. L. Acerini, and D. B. Dunger Dose-Dependent Effects of Recombinant Human Insulin-Like Growth Factor (IGF)-I/IGF Binding Protein-3 Complex on Overnight Growth Hormone Secretion and Insulin Sensitivity in Type 1 Diabetes J. Clin. Endocrinol. Metab., September 1, 2004; 89(9): 4634 - 4641. [Abstract] [Full Text] [PDF]

				M. Haluzik, S. Yakar, O. Gavrilova, J. Setser, Y. Boisclair, and D. LeRoith Insulin Resistance in the Liver-Specific IGF-1 Gene-Deleted Mouse Is Abrogated by Deletion of the Acid-Labile Subunit of the IGF-Binding Protein-3 Complex: Relative Roles of Growth Hormone and IGF-1 in Insulin Resistance Diabetes, October 1, 2003; 52(10): 2483 - 2489. [Abstract] [Full Text] [PDF]

				C. Livingstone and G. A. Ferns Review: Insulin-like growth factor-related proteins and diabetic complications The British Journal of Diabetes & Vascular Disease, September 1, 2003; 3(5): 326 - 331. [Abstract] [PDF]