Protein turnover in skeletal muscle of the diabetic rat: activation of ubiquitin-dependent proteolysis.
Induction of experimental insulin-deficiency by a single administration of streptozotocin to rats resulted in substantial changes in heart and skeletal muscle size and protein content. This was accompanied by a marked loss of total body (carcass) nitrogen and raised concentrations of circulating branched-chain amino acids. These changes were related to alterations in protein turnover in skeletal muscle. Thus, the diabetic animals showed changes in both the fractional protein rates of synthesis (decreased by 37%) and degradation (increased by 141%). The increased protein degradation observed in the muscle of the diabetic animals was associated only with an increase in the expression of the genes controlling ubiquitin-dependent proteolysis. It may be suggested that the hormonal changes associated with the diabetic state play an important role in the regulation of the activity of the ubiquitin-dependent proteolytic system in skeletal muscle, highlighting the major role of this system in the diabetes-related cachexia.
Rodríguez
T
T
Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain.
Busquets
S
S
Alvarez
B
B
Carb N
Agell
N
N
Lpez-Soriano
F J
FJ
Argilś
J M
JM
D020155:3-Hydroxybutyric Acid / Q000097:blood; D000090:Acetoacetates / Q000097:blood; D000273:Adipose Tissue / Q000254:growth & development; D000818:Animals; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005260:Female; D006868:Hydrolysis; D006943:Hyperglycemia / Q000097:blood; D007328:Insulin / Q000097:blood; D007532:Isoleucine / Q000378:metabolism; D007668:Kidney / Q000254:growth & development; D007930:Leucine / Q000378:metabolism; D008099:Liver / Q000254:growth & development; D008112:Liver Glycogen / Q000378:metabolism; D008762:Methylhistidines / Q000378:metabolism; D024510:Muscle Development; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000254:growth & development / Q000378:metabolism*; D009929:Organ Size; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014452:Ubiquitins / Q000235:genetics / Q000502:physiology; D014633:Valine / Q000378:metabolism
D000090:Acetoacetates; D007328:Insulin; D008112:Liver Glycogen; D008762:Methylhistidines; D009124:Muscle Proteins; D012333:RNA, Messenger; D014452:Ubiquitins; D007532:Isoleucine; C016635:acetoacetic acid; D007930:Leucine; D014633:Valine; C028118:3-methylhistidine; D020155:3-Hydroxybutyric Acid