We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
RBP4 Expression in Skeletal Muscle Correlates Highly with Insulin Resistance and Is Differentially Regulated by Exercise in Normal Versus Insulin Resistant Subjects.
- Authors
Graham, Timothy E.; Brandauer, Josef; Oberbach, Andreas; Bluher, Matthias; Goodyear, Laurie J.; Kahn, Barbara B.
- Abstract
Serum RBP4 levels correlate highly with insulin resistance and associated metabolic abnormalities. RBP4 overexpression in mice causes insulin resistance. Chronic exercise training that improves insulin sensitivity in insulin resistant human subjects lowers serum RBP4. Liver is considered the primary source of circulating RBP4 but adipose tissue may also produce RBP4 in insulin resistance. RBP4 mRNA is detected in cardiac and skeletal muscle, but it is not known whether muscle contributes to circulating RBP4 levels. Our aims were to determine: (1) whether RBP4 expression is altered in muscle in subjects with impaired glucose tolerance (IGT) or type 2 diabetes (T2D) and (2) whether RBP4 is regulated by chronic or acute exercise. RBP4 mRNA in quadriceps biopsies from IGT or T2D subjects was increased ∼250-fold (p<0.0001) at baseline relative to normal glucose tolerant control subjects. Exercise training for 1 month improved insulin sensitivity (measured by clamp) and lowered muscle RBP4 mRNA in the majority of IGT/T2D subjects. These decreases in muscle RBP4 mRNA correlated highly with decreases in serum RBP4 (R=0.86, p<0.0001) and inversely with changes in insulin sensitivity (R= -0.65, p<0.0001). In contrast, 1 mo of exercise training in lean, normoglycemic control subjects increased serum RBP4 and muscle RBP4 mRNA∼2-fold and ∼30-fold, respectively (p<0.0001), although mRNA was still only ∼8% of IGT/T2D levels. After 6 mo of training, serum RBP4 levels returned to baseline in controls. Studies of acute exercise in untrained control subjects demonstrated that exercise for 180 min at ∼70% VO[sub 2]max increased muscle RBP4 mRNA 9-fold (p=0.001) and serum RBP4 levels by 70% (p<0.05). Similarly, acute treadmill exercise in rats increased muscle RBP4 mRNA ∼5-fold and serum RBP4 40% with no change in liver or adipose tissue RBP4 mRNA. The amount of RBP4 secreted from soleus muscle ex vivo was greater than from the same amount of fat. These results show: (1) In IGT/T2D subjects, exercise training-induced decreases in muscle RBP4 mRNA correlate inversely with changes in insulin sensitivity; (2) in normal subjects, exercise training increases muscle RBP4; and (3) acute exercise-induced increases of RBP4 in serum correspond to increased RBP4 mRNA in muscle but not in other tissues. These findings suggest that RBP4 may be a novel muscle-secreted signal regulating fuel homeostasis in exercise.
- Subjects
GENE expression; CARRIER proteins; VITAMIN A; MUSCLES; INSULIN resistance; EXERCISE
- Publication
Diabetes, 2007, Vol 56, pA38
- ISSN
0012-1797
- Publication type
Article