Circulating levels of insulin-like growth factor-II/mannose-6-phosphate receptor in obesity and type 2 diabetes.
OBJECTIVE
The extracellular domain of the insulin-like growth factor II/mannose-6-phosphate receptor (IGF-II/M6P-R) is present in the circulation, but its relationship with plasma IGF-II is largely unknown. As IGF-II appears to be nutritionally regulated, we studied the impact of obesity, type 2 diabetes (T2D) and weight loss on circulating levels of IGF-II and its soluble receptor.


METHODS
Twenty-three morbidly obese non-diabetic subjects were studied before and after gastric banding (GB), reducing their BMI from 59.3+/-1.8 to 52.7+/-1.6 kg/m(2). Lean controls (n=10, BMI 24.2+/-0.5 kg/m(2)), moderately obese controls (n=21, BMI 31.8+/-1.0 kg/m(2)) and obese T2D patients (n=20, BMI 32.3+/-0.8 kg/m(2)) were studied before and after a hyperinsulinaemic euglycaemic clamp.


RESULTS
Morbidly obese subjects had elevated IGF-II/M6P-R and IGF-II levels, which both decreased following GB (IGF-II/M6P-R: from 0.97+/-0.038 to 0.87+/-0.030 nmol/l, P=0.001; IGF-II: from 134+/-7 to 125+/-6 nmol/l, P=0.01), as did fasting plasma glucose and insulin (P<0.05). However, the metabolic parameters correlated with neither IGF-II nor IGF-II/M6P-R. Obese diabetics had increased IGF-II/M6P-R as compared with lean and obese controls (0.82+/-0.031 vs. 0.70+/-0.033 vs. 0.74+/-0.026 nmol/l; P<0.03) and levels were unaffected by clamp. In the latter cohort, IGF-II/M6P-R but not IGF-II correlated with HbA1c, and fasting plasma C-peptide, insulin and glucose (0.34<r<0.45; P<0.05). In all subjects, BMI correlated with IGF-II/M6P-R (r=0.57; P<0.001) and IGF-II (r=0.39; P<0.005). IGF-II/M6P-R and IGF-II were not associated.


CONCLUSIONS
Serum IGF-II/M6P-R is up-regulated in morbid obesity, down-regulated by weight loss and elevated in moderately obese T2D. However, although plasma IGF-II was also reduced following GB, the two peptides were not statistically correlated. No acute effect of insulin was seen. These findings indicate that the IGF-II/M6P-R is nutritionally regulated, independently of IGF-II.
Jeyaratnaganthan
Nilani
N
The Medical Research Laboratories, Clinical Institute of Medicine & Medical Department M, Aarhus University Hospital, DK-8000 Aarhus C, Denmark.
Højlund
Kurt
K
Kroustrup
Jens Peter
JP
Larsen
Jens Fromholt
JF
Bjerre
Mette
M
Levin
Klavs
K
Beck-Nielsen
Henning
H
Frago
Susana
S
Hassan
A Bassim
AB
Flyvbjerg
Allan
A
Frystyk
Jan
J
D001774:Blood Chemical Analysis; D016022:Case-Control Studies; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000378:metabolism; D015391:Gastroplasty / Q000534:rehabilitation; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000032:analysis / Q000378:metabolism; D009747:Nutritional Physiological Phenomena; D009765:Obesity / Q000097:blood* / Q000378:metabolism / Q000601:surgery; D017527:Receptor, IGF Type 2 / Q000032:analysis / Q000097:blood* / Q000378:metabolism; D013851:Thinness / Q000097:blood / Q000378:metabolism; D054928:Validation Studies as Topic; D015431:Weight Loss / Q000502:physiology
D017527:Receptor, IGF Type 2; D007335:Insulin-Like Growth Factor II