Activity of insulin receptor kinase and glycogen synthase in skeletal muscle from patients with chronic renal failure.
To examine subcellular mechanisms behind the pathogenesis of peripheral insulin resistance in chronic uremic patients, insulin receptor function and glycogen synthase activity were studied in biopsies of skeletal muscle obtained during renal transplant surgery in 9 non-diabetic uremic patients. The results were compared with values obtained in an age- and sex-matched group of subjects with normal renal function, undergoing surgery for urological or gynecological diseases. The recovery of solubilized, wheat germ agglutinin-purified insulin receptors from skeletal muscle was increased among the uremic patients: 49.3 +/- 6.1 vs 31.4 +/- 2.8 fmol/100 mg muscle in healthy controls (p less than 0.03). Basal as well as insulin-stimulated kinase activities of the insulin receptors, expressed as phosphorylation of the synthetic peptide poly(Glu-Tyr(4:1] were similar. In addition, the maximal activity of the glycogen synthase was enhanced in uremic muscle: 26.6 +/- 2.8 vs 19.5 +/- 1.8 nmol.(mg protein)-1.min-1 (p less than 0.05), whereas the half-maximal activation constant for glucose-6-phosphate was identical in the two groups. Likewise, the muscle glycogen concentrations were similar in the uremic patients and the normal controls. In conclusion, our data suggest that neither impaired insulin receptor function nor a reduced maximal glycogen synthase activity of skeletal muscle are involved in the pathogenesis of the insulin resistance of patients with chronic renal failure.
Bak
J F
JF
Department of Endocrinology and Internal Medicine, Aarhus Amtssygehus, Denmark.
Schmitz
O
O
Sørensen
S S
SS
Frøkjaer
J
J
Kjaer
T
T
Pedersen
O
O
D000328:Adult; D005260:Female; D006003:Glycogen / Q000378:metabolism; D006006:Glycogen Synthase / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance; D007676:Kidney Failure, Chronic / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000201:enzymology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011972:Receptor, Insulin / Q000378:metabolism
D006003:Glycogen; D006006:Glycogen Synthase; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin