Central and opposing effects of IGF-I and IGF-binding protein-3 on systemic insulin action

Radhika H. Muzumdar, Xiaohui Ma, Sigal Fishman, Xiaoman Yang, Gil Atzmon, Patricia Vuguin, Francine H. Einstein, David Hwang, Pinchas Cohen, Nir Barzilai

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

IGF-I is recognized as an insulin sensitizer at the liver and muscle, while recent evidence suggests that IGF-binding protein (IGFBP)-3 acts as an insulin antagonist. As there is a paucity of IGF-I receptors in the liver and as the IGF-IGFBP system in the central nervous system is emerging as physiologically relevant, we examined whether the effects of IGF-I and IGFBP-3 on insulin action are mediated through central mechanisms. Intracerebroventricular (ICV) infusion of IGF-I during the insulin clamp (3 mU·kg-1·min -1) resulted in significant improvement in hepatic insulin action (50%, P < 0.05). In contrast, ICV infusion of IGFBP-3 significantly impaired insulin action at the liver (45% increase in hepatic glucose production, P < 0.01). While IGF-I marginally increased peripheral glucose uptake, IGFBP-3 significantly decreased peripheral glucose uptake (∼30%, P < 0.01). As the nuclear localization signal mutant IGFBP-3, which has a normal affinity to IGFs but binds other IGFBP-3 partners poorly and fails to normally internalize, has reduced central activity on metabolism, we conclude that the effects of IGFBP-3 on the hypothalamus involve activity mediated by interfacing with other molecules in addition to IGFs. Marked, opposing, and independent physiological effects of IGF-I and IGFBP-3 through central mechanisms may have implications on potential strategies in specific modulation of peripheral insulin action.

Original languageEnglish (US)
Pages (from-to)2788-2796
Number of pages9
JournalDiabetes
Volume55
Issue number10
DOIs
StatePublished - Oct 2006

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Insulin-Like Growth Factor Binding Protein 3
Insulin-Like Growth Factor I
Insulin
Liver
Intraventricular Infusions
Glucose
Insulin Antagonists
Nuclear Localization Signals
Insulin-Like Growth Factor Binding Proteins
IGF Type 1 Receptor
Mutant Proteins
Hypothalamus
Central Nervous System
Muscles

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Muzumdar, R. H., Ma, X., Fishman, S., Yang, X., Atzmon, G., Vuguin, P., ... Barzilai, N. (2006). Central and opposing effects of IGF-I and IGF-binding protein-3 on systemic insulin action. Diabetes, 55(10), 2788-2796. https://doi.org/10.2337/db06-0318

Central and opposing effects of IGF-I and IGF-binding protein-3 on systemic insulin action. / Muzumdar, Radhika H.; Ma, Xiaohui; Fishman, Sigal; Yang, Xiaoman; Atzmon, Gil; Vuguin, Patricia; Einstein, Francine H.; Hwang, David; Cohen, Pinchas; Barzilai, Nir.

In: Diabetes, Vol. 55, No. 10, 10.2006, p. 2788-2796.

Research output: Contribution to journalArticle

Muzumdar, RH, Ma, X, Fishman, S, Yang, X, Atzmon, G, Vuguin, P, Einstein, FH, Hwang, D, Cohen, P & Barzilai, N 2006, 'Central and opposing effects of IGF-I and IGF-binding protein-3 on systemic insulin action', Diabetes, vol. 55, no. 10, pp. 2788-2796. https://doi.org/10.2337/db06-0318
Muzumdar RH, Ma X, Fishman S, Yang X, Atzmon G, Vuguin P et al. Central and opposing effects of IGF-I and IGF-binding protein-3 on systemic insulin action. Diabetes. 2006 Oct;55(10):2788-2796. https://doi.org/10.2337/db06-0318
Muzumdar, Radhika H. ; Ma, Xiaohui ; Fishman, Sigal ; Yang, Xiaoman ; Atzmon, Gil ; Vuguin, Patricia ; Einstein, Francine H. ; Hwang, David ; Cohen, Pinchas ; Barzilai, Nir. / Central and opposing effects of IGF-I and IGF-binding protein-3 on systemic insulin action. In: Diabetes. 2006 ; Vol. 55, No. 10. pp. 2788-2796.
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