In chronic uremia, insulin activates receptor kinase but not pyruvate dehydrogenase.
We studied in vivo biochemical effects of insulin in the skeletal muscle of chronically uremic and control rats. The rate of disappearance of blood glucose (determined with a short intravenous test) was reduced by 38% in uremia (p less than 0.05). Intraperitoneal treatment with insulin plus glucose for 30 min caused a 3-fold increase in the activity of insulin receptor tyrosine kinase in the skeletal muscle of both rat groups. Conversely, pyruvate dehydrogenase activity increased by 115% in controls but only by 26% in uremics (p less than 0.01). Exercise (swimming for 30 min) increased muscle pyruvate dehydrogenase activity approximately 2-fold in both groups of animals. These experiments show that in uremic rats, insulin binds normally to its muscle receptors and adequately activates receptor tyrosine kinase but fails to activate an otherwise responsive pyruvate dehydrogenase.
Contreras
I
I
Division de Nefrología, Hospital Universitario de Caracas, Venezuela.
Caro
J F
JF
Aveledo
L
L
Diaz
K
K
Durrego
P
P
Weisinger
J R
JR
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004789:Enzyme Activation; D005951:Glucose Tolerance Test; D007328:Insulin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000201:enzymology*; D008297:Male; D009132:Muscles / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011972:Receptor, Insulin / Q000302:isolation & purification / Q000378:metabolism*; D012016:Reference Values; D014511:Uremia / Q000097:blood / Q000201:enzymology*
D001786:Blood Glucose; D007328:Insulin; D011768:Pyruvate Dehydrogenase Complex; C008147:insulin, iodo-; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin