Distribution of peroxisome proliferator-activated receptors (PPARs) in human skeletal muscle and adipose tissue: Relation to insulin action

Abstract

Aims/hypothesis. To evaluate the tissue distribution and possible role of the peroxisome proliferator-activated receptors (PPARs) in insulin action in fat and muscle biopsy specimens from lean, obese and subjects with Type II (non-insulin-dependent) diabetes mellitus. Methods. We measured PPARα, PPARβ(δ) and PPARγ protein expression by western blot analysis. The PPARγ protein was also measured in muscle before and after 3-h hyperinsulinaemic (300 mU · m-2 · min-1) euglycaemic clamps. Results. The PPARα protein was expressed preferentially in muscle relative to fat (more than sevenfold). The PPARβ protein was similar in fat and muscle. The amount of PPARγ protein found in muscle was, on average, two-thirds of that present in fat. There was no statistically significant difference between non-diabetic and diabetic subjects in baseline (preclamp) muscle PPAR (α, β or γ) protein expression. Subgroup analysis showed, however, significantly higher PPARγ protein in the most insulin resistant diabetic subjects with glucose disposal rates of 3-6 mg · kg-1 · min-1 compared with their age and weight matched counterparts with glucose disposal rates of 6-9 (147 ± 23 vs 88 ± 10 AU/μg protein, p ≤ 0.01 in diabetic and vs 94 ± 15, p ≤ 0.04 in non- diabetic subjects). Muscle PPARγ protein and glucose disposal rates were inversely correlated in diabetic subjects (r = -0.47, p ≤ 0.05). Conclusion/interpretation. All PPARs (α, β or γ) are present in skeletal muscle and adipose tissue with different relative distributions. The PPARγ protein is abundant in skeletal muscle as well as adipose tissue. The altered expression of skeletal muscle PPARγ is consistent with a role for this nuclear protein in the impaired insulin action of Type II diabetes.