Deficiency in phosphorylase phosphatase activity despite elevated protein phosphatase type-1 catalytic subunit in skeletal muscle from insulin-resistant subjects.
AUTOR(ES)
Nyomba, B L
RESUMO
Glycogen synthase is activated by protein phosphatase type-1 (PP-1). The spontaneous PP-1 activity accounts for only a small fraction of total PP-1 activity, which can be exposed by trypsin digestion of inhibitor proteins in the presence of Mn2+. We determined total PP-1 activity in muscle biopsies from insulin-sensitive and -resistant nondiabetic Pima Indians. Inhibitor-2 sensitive PP-1 represented 90% of total phosphatase activity. Spontaneous and total PP-1 activities were reduced in insulin resistant subjects (P less than 0.05-0.01), suggesting that the reduced PP-1 activity is not the result of inhibition by trypsin-labile phosphatase regulatory subunits. This difference was further investigated by Western blots using two different antibodies. An antibody raised against the rabbit muscle PP-1 catalytic subunit was used to analyze muscle extracts concentrated by DEAE-Sepharose adsorption. An antibody raised against a peptide derived from the COOH-terminal end of the PP-1 catalytic subunit was used to analyze crude muscle extracts. Both antibodies recognized a PP-1 catalytic subunit of approximately 33 kD, which unexpectedly was more abundant in insulin-resistant subjects (P less than 0.05-0.01). The increase in the tissue PP-1 protein content may be a response to compensate for the impairment in the enzyme activity.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=295665Documentos Relacionados
- Defective insulin response of phosphorylase phosphatase in insulin-resistant humans.
- Alterations in skeletal muscle protein-tyrosine phosphatase activity and expression in insulin-resistant human obesity and diabetes.
- Defect in skeletal muscle phosphatidylinositol-3-kinase in obese insulin-resistant mice.
- Abnormal regulation of ribosomal protein S6 kinase by insulin in skeletal muscle of insulin-resistant humans.
- Glycogen synthase and phosphofructokinase protein and mRNA levels in skeletal muscle from insulin-resistant patients with non-insulin-dependent diabetes mellitus.