We examined the possibility that protein kinase C (PKC) is chronically activated and may contribute to impaired glycogen synthesis and insulin resistance in soleus muscles of hyperinsulinemic type II diabetic Goto-Kakizaki (GK) rats. Relative to nondiabetic controls, PKC enzyme activity and levels of immunoreactive PKC-α, β, є, and delta were increased in membrane fractions and decreased cytosolic fractions of GK soleus muscles. In addition, PKC-θ levels were decreased in both membrane and cytosol fractios, whereas PKC-ζ levels were not changed in either fraction in GK soleus muscles. These increases in membrane PKC (α, β, є, and δ) could not be accounted for by alterations in PKC mRNA or total PKC levels but were associated with increases in membrane diacylglycerol (DAG) and therefore appeared to reflect translocative activation of PKC. In evaluation of potential causes for persistent PKC activation, membrane PKC levels were decreased in soleus muscles of hyperglycemic streptozotocin (STZ)-induced diabetic rats; thus, a role for simple hyperglycemia as a cause of PKC activation in GK rats was not evident in the STZ model. In support of the possibility that hyperinsulinemia contributed to PKC activation in GK soleus muscles, we found that DAG levels were increased, and PKC was translocated, in soleus muscles of both (1) normoglycemic hyperinsulinemic obese/aged rats and (2) mildly hyperglycemic hyperinsulinemic obese/Zucker rats. In keeping with the possibility that PKC activation may contribute to impaired glycogen synthase activation in GK muscles, phorbol esters inhibited, and a PKC inhibitor, RO 31-8220, increased insulin effects on glycogen synthesis in soleus muscles incubated in vitro. Our findings suggested that: (1) hyperinsulinemia, as observed in type II diabetic GK rats and certain genetic and nongenetic forms of obesity in rats, is associated with persistent translocation and activation of PKC in soleus muscles, and (2) this persistent PKC activation may contribute to impaired glycogen synthesis and insulin resistance.
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Original Articles|
October 01 1996
Chronic Activation of Protein Kinase C in Soleus Muscles and Other Tissues of Insulin-Resistant Type II diabetic Goto-Kakizaki (GK), Obese/Aged, and Obese/Zucker Rats: A Mechanism For Inhibiting Glycogen Synthesis
Antoine Avignon;
Antoine Avignon
J. A. Haley Veterans' Hospital and the Departments of Internal Medicine and Biochemistry, University of S. Florida College of Medicine, University of S. Florida
Tampa, Florida
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Kouji Yamada;
Kouji Yamada
J. A. Haley Veterans' Hospital and the Departments of Internal Medicine and Biochemistry, University of S. Florida College of Medicine, University of S. Florida
Tampa, Florida
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Xiaoping Zhou;
Xiaoping Zhou
J. A. Haley Veterans' Hospital and the Departments of Internal Medicine and Biochemistry, University of S. Florida College of Medicine, University of S. Florida
Tampa, Florida
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Barbara Spencer;
Barbara Spencer
J. A. Haley Veterans' Hospital and the Departments of Internal Medicine and Biochemistry, University of S. Florida College of Medicine, University of S. Florida
Tampa, Florida
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Osvaldo Cardona;
Osvaldo Cardona
J. A. Haley Veterans' Hospital and the Departments of Internal Medicine and Biochemistry, University of S. Florida College of Medicine, University of S. Florida
Tampa, Florida
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Shereen Saba-Siddique;
Shereen Saba-Siddique
J. A. Haley Veterans' Hospital and the Departments of Internal Medicine and Biochemistry, University of S. Florida College of Medicine, University of S. Florida
Tampa, Florida
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Lamar Galloway;
Lamar Galloway
J. A. Haley Veterans' Hospital and the Departments of Internal Medicine and Biochemistry, University of S. Florida College of Medicine, University of S. Florida
Tampa, Florida
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Mary L Standaert;
Mary L Standaert
J. A. Haley Veterans' Hospital and the Departments of Internal Medicine and Biochemistry, University of S. Florida College of Medicine, University of S. Florida
Tampa, Florida
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Robert V Farese
Robert V Farese
J. A. Haley Veterans' Hospital and the Departments of Internal Medicine and Biochemistry, University of S. Florida College of Medicine, University of S. Florida
Tampa, Florida
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Address correspondence and reprint requests to Dr. Robert V. Farese, Research Service (VAR 151), J.A. Haley Veterans' Hospital, 13000 Bruce Downs Blvd., Tampa, FL 33612.
Diabetes 1996;45(10):1396–1404
Article history
Received:
November 21 1995
Revision Received:
May 09 1996
Accepted:
May 09 1996
PubMed:
8826977
Citation
Antoine Avignon, Kouji Yamada, Xiaoping Zhou, Barbara Spencer, Osvaldo Cardona, Shereen Saba-Siddique, Lamar Galloway, Mary L Standaert, Robert V Farese; Chronic Activation of Protein Kinase C in Soleus Muscles and Other Tissues of Insulin-Resistant Type II diabetic Goto-Kakizaki (GK), Obese/Aged, and Obese/Zucker Rats: A Mechanism For Inhibiting Glycogen Synthesis. Diabetes 1 October 1996; 45 (10): 1396–1404. https://doi.org/10.2337/diab.45.10.1396
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