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

• DOI: 10.2337/diab.45.10.1396
• Publication Date: 2013-09-19T17:42:54Z
• Authors: Antoine Avignon; Kouji Yamada; Xiaoping Zhou; Barbara Spencer; Osvaldo Cardona; Shereen Saba-Sidd...; Lamar Galloway; Mary L Standaert; Robert V Farese
• Keywords: Hyperinsulinemia

We examined the possibility that protein kinase C (PKC) is chronically activated and may contribute to impaired glycogen synthesis insulin resistance in soleus muscles of hyperinsulinemic type II diabetic Goto-Kakizaki (GK) rats. Relative nondiabetic controls, PKC enzyme activity levels immunoreactive PKC-α, β, є, delta were increased membrane fractions decreased cytosolic GK muscles. In addition, PKC-θ both cytosol fractios, whereas PKC-ζ not changed either fraction These increases (α, δ) could be accounted for by alterations mRNA or total but associated with diacylglycerol (DAG) therefore appeared reflect translocative activation PKC. evaluation potential causes persistent activation, hyperglycemic streptozotocin (STZ)-induced rats; thus, a role simple hyperglycemia as cause rats was evident STZ model. support hyperinsulinemia contributed muscles, we found DAG increased, translocated, (1) normoglycemic obese/aged (2) mildly obese/Zucker keeping synthase phorbol esters inhibited, inhibitor, RO 31-8220, effects on incubated vitro. Our findings suggested that: hyperinsulinemia, observed certain genetic nongenetic forms obesity rats, translocation this resistance.