PROTEIN-KINASE-C ISOFORM-EPSILON, ISOFORM-ETA, ISOFORM-DELTA AND ISOFORM-ZETA IN MURINE ADIPOCYTES - EXPRESSION, SUBCELLULAR-LOCALIZATION AND TISSUE-SPECIFIC REGULATION IN INSULIN-RESISTANT STATES

The Ca2(+)-insensitive protein kinase C (PKC) isoforms epsilon, eta, d elta, and zeta are possible direct downstream targets of phosphatidyli nositol 3-kinase (PI3-K), and might therefore be involved in insulin s ignalling. Although isoform-specific changes in PKC expression have be en reported for skeletal muscle and liver in insulin-resistant states, little is known about these isoforms in adipocytes. Therefore we stud ied (1) expression and subcellular localization of these isoforms in m urine adipocytes, (2) translocation of specific isoforms to membranes in response to treatment with insulin and phorbol 12-myristate 13-acet ate (PMA) and (3) regulation of expression in insulin-resistant states . The PKC isoforms epsilon, eta, delta and zeta are expressed in adipo cytes. Immunoreactivity for all isoforms is higher in the membranes th an in the cytosol, but subcellular fractionation by differential centr ifugation shows an isoform-specific distribution within the membrane f ractions. PMA treatment of adipocytes induces translocation of PKC-eps ilon and -delta from the cytosol to the membrane fractions. Insulin tr eatment does not alter the subcellular distribution of any of the isof orms. 3T3-L1 adipocytes express PKC-epsilon and -zeta, and PKC-epsilon expression increases with differentiation from preadipocytes to adipo cytes. PKC-epsilon expression decreases in an adipose-specific and age /obesity-dependent manner in two insulin-resistant models, the brown-a dipose-tissue-deficient mouse and db/db mouse compared with control mi ce. We conclude that, although none of the isoforms investigated seems to be activated by insulin, the decrease in PKC-E expression might co ntribute to metabolic alterations in adipocytes associated with insuli n resistance and obesity.