The role of insulin-like growth factor (IGF) binding protein-2 in the insulin-mediated decrease in IGF-I bioactivity.
BACKGROUND
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.


METHODS
The study was conducted at an endocrinology center.


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.
Arafat
Ayman M
AM
Department of Endocrinology, Diabetes, and Nutrition, Charité-University Medicine Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany. ayman.arafat@charite.de
Weickert
Martin O
MO
Frystyk
Jan
J
Spranger
Joachim
J
Schöfl
Christof
C
Möhlig
Matthias
M
Pfeiffer
Andreas F H
AF
D000328:Adult; D000368:Aged; D000818:Animals; D015415:Biomarkers; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D005260:Female; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006728:Hormones / Q000097:blood; D006801:Humans; D007328:Insulin / Q000502:physiology*; D007333:Insulin Resistance / Q000235:genetics* / Q000502:physiology*; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D008055:Lipids / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics / Q000503:physiopathology; D051379:Mice; D008875:Middle Aged; D009765:Obesity / Q000235:genetics / Q000503:physiopathology; D055815:Young Adult
D015415:Biomarkers; D001786:Blood Glucose; D006728:Hormones; D007328:Insulin; D018971:Insulin-Like Growth Factor Binding Protein 2; D008055:Lipids; D007334:Insulin-Like Growth Factor I