Distribution of peroxisome proliferator-activated receptors (PPARs) in human skeletal muscle and adipose tissue: relation to insulin action.
OBJECTIVE
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 PPAR alpha, PPAR beta (delta) and PPAR gamma protein expression by western blot analysis. The PPAR gamma protein was also measured in muscle before and after 3-h hyperinsulinaemic (300 mU.m-2.min-1) euglycaemic clamps.


RESULTS
The PPAR alpha protein was expressed preferentially in muscle relative to fat (more than sevenfold). The PPAR beta protein was similar in fat and muscle. The amount of PPAR gamma 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 (alpha, beta or gamma) protein expression. Subgroup analysis showed, however, significantly higher PPAR gamma 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/microgram protein, p < or = 0.01 in diabetic and vs 94 +/- 15, p < or = 0.04 in non-diabetic subjects). Muscle PPAR gamma protein and glucose disposal rates were inversely correlated in diabetic subjects (r = -0.47, p < or = 0.05).


CONCLUSIONS
All PPARs (alpha, beta or gamma) are present in skeletal muscle and adipose tissue with different relative distributions. The PPAR gamma protein is abundant in skeletal muscle as well as adipose tissue. The altered expression of skeletal muscle PPAR gamma is consistent with a role for this nuclear protein in the impaired insulin action of Type II diabetes.
Loviscach
M
M
VA San Diego Healthcare System, California 92161, USA.
Rehman
N
N
Carter
L
L
Mudaliar
S
S
Mohadeen
P
P
Ciaraldi
T P
TP
Veerkamp
J H
JH
Henry
R R
RR
D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D002352:Carrier Proteins / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D006801:Humans; D007328:Insulin / Q000494:pharmacology / Q000502:physiology; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D018996:Myelin P2 Protein / Q000378:metabolism; D009363:Neoplasm Proteins; D009765:Obesity / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D012016:Reference Values; D014018:Tissue Distribution; D014157:Transcription Factors / Q000378:metabolism*; D025521:Tumor Suppressor Proteins
D002352:Carrier Proteins; C107608:FABP7 protein, human; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D007328:Insulin; D018996:Myelin P2 Protein; D009363:Neoplasm Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins