Protein kinase Cθ expression is increased upon differentiation of human skeletal muscle cells:: Dysregulation in type 2 diabetic patients and a possible role for protein kinase Cθ in insulin-stimulated glycogen synthase activity

Protein kinase C (PKC theta) is a key enzyme in regulating a variety of cellular functions, including growth and differentiation. PKC theta is the most abundant PKC isoform expressed in skeletal muscle; however, its role in differentiation and metabolism is not clear. We examined the effect of muscle cell differentiation on PKC theta expression in human skeletal muscle cells from normal and type 2 diabetic subjects. Low levels of PKC theta messenger RNA (mRNA) and protein were detected in human myoblasts from both types of subjects. Upon differentiation into myotubes, PKC theta mRNA and protein were increased 12-fold in myotubes from normal subjects. In human skeletal muscle cells obtained from type 2 diabetic subjects, increases in PKC theta mRNA and protein were not observed upon differentiation into myotubes al-though expression of other markers of differentiation and fusion increased. Cells from type 2 diabetic subjects also exhibited decreased insulin-stimulated glycogen synthase activity. To determine whether the up-regulation of PKC theta was important for the metabolic actions of insulin, PKC theta was overexpressed in L6 rat skeletal muscle cells. Increased expression of PKC theta occurred with differentiation of skeletal muscle myoblasts to myotubes. Glycogen synthase activity was further increased in L6 myotubes stably transfected with the complementary DNA for PKC theta. The decreased expression of PKC theta found in cells from type 2 diabetic subjects may be linked to insulin resistance and decreased glycogen synthase activity.