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Protein kinase C (PKCtheta) is a key enzyme in regulating a variety of cellular functions, including growth and differentiation. PKCtheta 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 PKCtheta expression in human skeletal muscle cells from normal and type 2 diabetic subjects. Low levels of PKCtheta messenger RNA (mRNA) and protein were detected in human myoblasts from both types of subjects. Upon differentiation into myotubes, PKCtheta 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 PKCtheta mRNA and protein were not observed upon differentiation into myotubes although 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 PKCtheta was important for the metabolic actions of insulin, PKCtheta was overexpressed in L6 rat skeletal muscle cells. Increased expression of PKCtheta 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 PKCtheta. The decreased expression of PKCtheta found in cells from type 2 diabetic subjects may be linked to insulin resistance and decreased glycogen synthase activity.

Although vitamin E has been recognized as a requirement for normal testicular function for more than 50 yr, the functional role of this fat soluble vitamin in the maintenance of spermatogenesis has not been clarified. Vitamin E deficiency has a deleterious effect on germ cell proliferation and differentiation in the rat and a variety of other animal species. The potential effect of vitamin E on the sensitivity of the hypothalmo-hypophyseal-gonadal feedback system has not been previously evaluated. Therefore, serum testosterone concentrations, androgen function in maintaining seminal vesicle weight, and citrate synthesis, as well as the circulating amounts of FSH, were determined in rats fed semipurified diets with vitamin E, control, and without vitamin E, vitamin E-deficient. To assess dietary effects before, during, and after testicular degeneration, analyses were carried out on animals fed the diets starting at 3 weeks of age and continuing for 1 yr. The defect produced by vitamin E deficiency does not reflect impaired gonadotropin function. There are no effects of vitamin E deprivation on either serum levels of testosterone or on seminal vesicle weight and citrate content suggesting that the LH-testosterone feedback loop is not impaired. The feedback loop of FSH and inhibin also appears to be normal. Serum FSH concentrations are not elevated, although the testis is germ cell depleted. Comparison of the vitamin E-deficient model to other models of testicular degeneration suggests that the effect of vitamin E occurs directly or indirectly on the regulation of intratesticular factors which regulate specific steps of germ cell development.