Pro- and mature IGF-II during diet-induced weight loss in obese subjects.
BACKGROUND
In normal subjects up to 10% of circulating insulin-like growth factor II (IGF-II) consists of pro-IGF-II. However, its regulation and biological impact remains unknown. In obese subjects, serum free and total IGF-II are increased, and we therefore investigated the impact of obesity and diet on serum pro-IGF-II.


METHODS
Non-diabetic, obese subjects (n = 34) with a body mass index (BMI) of 38.9 +/- 0.5 kg/m2 were subjected to 8 weeks with very low calorie diet (800 kcal/day) followed by 12 weeks with a weight-stabilizing diet. Fasting serum was collected before the study, and after 8 and 20 weeks. Pro-IGF-II was determined after acid-gel chromatography using a novel, highly specific in-house assay, free and total IGFs were measured after ultrafiltration and acid-ethanol extraction, respectively, and IGF-binding proteins (IGFBPs) were measured with specific immunoassays.


RESULTS
Diet reduced BMI and fasting levels of insulin and glucose (P < 0.001). Serum pro-IGF-II was markedly reduced in obese subjects as compared with matched normal-weight controls (means and 95% confidence intervals: 93 microg/l (82-104 microg/l) versus 171 microg/l (152-192 microg/l), respectively; P < 0.001), and levels remained unchanged after the weight loss. In contrast, during the study period total and free IGF-II decreased (P < 0.05), whereas total IGF-I, IGFBP-1 and IGFBP-2 increased (P < 0.001). Serum free IGF-I remained unaltered. Cross-sectional and longitudinal correlation analyses showed that pro-IGF-II was closer and more consistently associated with IGF-I than IGF-II.


CONCLUSIONS
This study demonstrates that pro-IGF-II is reduced in obesity, in contrast to mature IGF-II. This indicates a hitherto unrecognized link between nutrition and pro-IGF-II. In addition, our data indicate that pro-IGF-II is regulated independently of mature IGF-II.
Espelund
Ulrick
U
Medical Research Laboratories, Clinical Institute and Medical Department C and M, Aarhus University Hospital, Aarhus C, Denmark. uen@studmed.au.dk
Bruun
Jens Meldgaard
JM
Richelsen
Bjørn
B
Flyvbjerg
Allan
A
Frystyk
Jan
J
D000328:Adult; D004038:Diet, Reducing; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood* / Q000276:immunology; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007335:Insulin-Like Growth Factor II; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000178:diet therapy*; D011498:Protein Precursors / Q000097:blood*; D012680:Sensitivity and Specificity
D018971:Insulin-Like Growth Factor Binding Protein 2; D011498:Protein Precursors; C066038:proinsulin-like growth factor II; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II