Effect of insulin on protein phosphatase 2A expression in muscle in type 2 diabetes.
BACKGROUND
Protein phosphatase 2A (PP2A) acts on a number of enzymes involved in the insulin regulation of glucose uptake and glycogen synthesis. This study was carried out to investigate the effect of insulin on PP2A expression in skeletal muscles of type 2 diabetic and control subjects.


METHODS
Ten type 2 diabetic and 10 matched, control subjects were studied using the euglycaemic-hyperinsulinaemic clamp technique combined with indirect calorimetry. Immunoreactive protein levels of the catalytic alpha subunit of PP2A (PP2A-C alpha) were measured in biopsies from the vastus lateralis muscle obtained in the basal and insulin-stimulated state.


RESULTS
In type 2 diabetic subjects insulin-mediated glucose disposal, glucose oxidation and nonoxidative glucose metabolism were reduced, whereas lipid oxidation was increased (all P < 0.05). Insulin down-regulated PP2A-C alpha expression in skeletal muscle of the control subjects (P < 0.05) but not in the type 2 diabetic subjects. In the control subjects, the insulin-mediated decrease in PP2A-C alpha correlated with the insulin-mediated increase in glucose disposal, glucose oxidation, nonoxidative glucose metabolism (all P < 0.05) and decrease in lipid oxidation (P < 0.01). In the type 2 diabetic subjects these relationships were absent.


CONCLUSIONS
Down-regulation of PP2A-C alpha expression by insulin in skeletal muscle seems to be associated with a normal insulin action on glucose storage, glucose and lipid oxidation. Impaired down-regulation of PP2A-C alpha expression by insulin may be a marker for insulin resistance and contribute to the pathogenesis of type 2 diabetes.
Højlund
K
K
Department of Endocrinology, Odense University Hospital, Odense C, Denmark. k.hojlund@dadlnet.dk
Poulsen
M
M
Staehr
P
P
Brusgaard
K
K
Beck-Nielsen
H
H
D015415:Biomarkers / Q000032:analysis; D002153:Calorimetry, Indirect; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology; D010749:Phosphoprotein Phosphatases / Q000032:analysis / Q000378:metabolism*; D054648:Protein Phosphatase 2; D018709:Statistics, Nonparametric
D015415:Biomarkers; D007004:Hypoglycemic Agents; D007328:Insulin; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; D005947:Glucose