CONTEXT: Insulin interacts with the GH-IGF system by a reciprocal regulation of IGF-binding proteins (IGFBP) and GH, which in turn regulate insulin sensitivity via bioactive IGF-I. This network is linked to metabolic syndrome and cardiovascular diseases. OBJECTIVE: We evaluated the effect of glucose and insulin on IGFBP-1-4, particularly IGFBP-2, in the regulation of bioactive IGF-I and its relation to insulin resistance. SETTING: The study was conducted at an endocrinology center. RESEARCH DESIGN AND METHODS: Twenty-four healthy subjects (12 men; aged 21-72 yr; body mass index 25.9 +/- 0.9 kg/m(2)) and 19 subjects with impaired glucose tolerance (IGT; eight men; aged 26-71 yr; body mass index 28.9 +/- 1.2 kg/m(2)) were prospectively studied using oral glucose tolerance test and hyperinsulinemic euglycemic clamp. RESULTS: During the clamp, insulin decreased IGF-I bioactivity in both IGT subjects and controls (-16.2 +/- 2.8 and -13.9 +/- 3.3%, respectively; P < 0.01). In addition, insulin increased IGFBP-2 and GH and decreased IGFBP-1 and -4 but did not alter total IGF-I, IGF-II, or IGFBP-3 levels. During the oral glucose tolerance test, GH and IGFBP-1 were markedly suppressed. Subjects with IGT showed more pronounced insulin resistance and lower GH, IGFBP-1, and IGFBP-2 levels (P < 0.05). In multiple regression analysis, IGFBP-2 was an independent predictor of insulin sensitivity (beta = 0.36, P < 0.05) and IGF-I bioactivity (beta = -0.5, P < 0.05). CONCLUSIONS: Our data indicate that insulin acutely decreases IGF-I bioactivity through differential modulation of IGFBPs. Furthermore, IGFBP-2 plays a central role in the insulin-IGF system cross talk and is closely linked to insulin resistance, thereby providing a further explanation for its association with the metabolic syndrome.
CONTEXT: Insulin interacts with the GH-IGF system by a reciprocal regulation of IGF-binding proteins (IGFBP) and GH, which in turn regulate insulin sensitivity via bioactive IGF-I. This network is linked to metabolic syndrome and cardiovascular diseases. OBJECTIVE: We evaluated the effect of glucose and insulin on IGFBP-1-4, particularly IGFBP-2, in the regulation of bioactive IGF-I and its relation to insulin resistance. SETTING: The study was conducted at an endocrinology center. RESEARCH DESIGN AND METHODS: Twenty-four healthy subjects (12 men; aged 21-72 yr; body mass index 25.9 +/- 0.9 kg/m(2)) and 19 subjects with impaired glucose tolerance (IGT; eight men; aged 26-71 yr; body mass index 28.9 +/- 1.2 kg/m(2)) were prospectively studied using oral glucose tolerance test and hyperinsulinemic euglycemic clamp. RESULTS: During the clamp, insulin decreased IGF-I bioactivity in both IGT subjects and controls (-16.2 +/- 2.8 and -13.9 +/- 3.3%, respectively; P < 0.01). In addition, insulin increased IGFBP-2 and GH and decreased IGFBP-1 and -4 but did not alter total IGF-I, IGF-II, or IGFBP-3 levels. During the oral glucose tolerance test, GH and IGFBP-1 were markedly suppressed. Subjects with IGT showed more pronounced insulin resistance and lower GH, IGFBP-1, and IGFBP-2 levels (P < 0.05). In multiple regression analysis, IGFBP-2 was an independent predictor of insulin sensitivity (beta = 0.36, P < 0.05) and IGF-I bioactivity (beta = -0.5, P < 0.05). CONCLUSIONS: Our data indicate that insulin acutely decreases IGF-I bioactivity through differential modulation of IGFBPs. Furthermore, IGFBP-2 plays a central role in the insulin-IGF system cross talk and is closely linked to insulin resistance, thereby providing a further explanation for its association with the metabolic syndrome.
Authors: Zeinab Sarem; Christiane Bumke-Vogt; Ayman M Mahmoud; Biruhalem Assefa; Martin O Weickert; Aikatarini Adamidou; Volker Bähr; Jan Frystyk; Matthias Möhlig; Joachim Spranger; Stefanie Lieske; Andreas L Birkenfeld; Andreas F H Pfeiffer; Ayman M Arafat Journal: J Clin Endocrinol Metab Date: 2017-09-01 Impact factor: 5.958
Authors: Jose Cordoba-Chacon; Manuel D Gahete; Ana I Pozo-Salas; Antonio Moreno-Herrera; Justo P Castaño; Rhonda D Kineman; Raúl M Luque Journal: Am J Physiol Endocrinol Metab Date: 2012-08-28 Impact factor: 4.310
Authors: Gang Xi; Melissa A Solum; Christine Wai; Laura A Maile; Clifford J Rosen; David R Clemmons Journal: Endocrinology Date: 2013-08-27 Impact factor: 4.736
Authors: Giovanni Vitale; Michael P Brugts; Giulia Ogliari; Davide Castaldi; Letizia M Fatti; Aimee J Varewijck; Steven W Lamberts; Daniela Monti; Laura Bucci; Elisa Cevenini; Francesco Cavagnini; Claudio Franceschi; Leo J Hofland; Daniela Mari; Joseph Janssen Journal: Aging (Albany NY) Date: 2012-09 Impact factor: 5.682