Retinol-binding protein 4 in twins: regulatory mechanisms and impact of circulating and tissue expression levels on insulin secretion and action.
OBJECTIVE
Retinol-binding protein (RBP) 4 is an adipokine of which plasma levels are elevated in obesity and type 2 diabetes. The aims of the study were to identify determinants of plasma RBP4 and RBP4 mRNA expression in subcutaneous adipose tissue (SAT) and skeletal muscle and to investigate the association between RBP4 and in vivo measures of glucose metabolism.


METHODS
The study population included 298 elderly twins (aged 62-83 years), with glucose tolerance ranging from normal to overt type 2 diabetes, and 178 young (aged 25-32 years) and elderly (aged 58-66 years) nondiabetic twins. Peripheral and hepatic insulin sensitivity was assessed by a euglycemic-hyperinsulinemic clamp, and beta-cell function was estimated from an intravenous glucose tolerance test.


RESULTS
The influence of environmental versus genetic factors in the regulation of plasma RBP4 increased with age. Plasma RBP4 was elevated in type 2 diabetes and increased with duration of disease. Plasma RBP4 correlated inversely with peripheral, but not hepatic, insulin sensitivity. However, the association disappeared after correction for covariates, including plasma adiponectin. Plasma retinol, and not RBP4, was inversely associated with insulin secretion. SAT RBP4 expression correlated positively with GLUT4 expression and inversely with glucose tolerance. Skeletal muscle RBP4 expression reflected intramuscular fat, and although it was suppressed by insulin, no association with insulin sensitivity was evident. RBP4 expression was not associated with circulatory RBP4.


CONCLUSIONS
In conclusion, our data indicate that RBP4 levels in plasma, skeletal muscle, and fat may be linked to insulin resistance and type 2 diabetes in a secondary and noncausal manner.
Steno Diabetes Center, Gentofte, Denmark. rrma@steno.dk
Rasmus
R
Ribel-Madsen
Martin
M
Friedrichsen
Allan
A
Vaag
Pernille
P
Poulsen
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D003924:Diabetes Mellitus, Type 2 / Q000097:blood; D004200:Diseases in Twins / Q000097:blood / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism; D009765:Obesity / Q000097:blood / Q000378:metabolism; D054839:Retinol-Binding Proteins, Plasma / Q000378:metabolism*; D050151:Subcutaneous Fat / Q000378:metabolism; D014427:Twins / Q000378:metabolism*
C101326:RBP4 protein, human; D054839:Retinol-Binding Proteins, Plasma