In the early and middle stages of diabetes in ZDF rats, 10 and 14 wk of age, respectively, GK expression is not higher when compared with their lean littermates, whereas the processes of GK activation in response to an elevated concentration of PG and P-INS, the dissociation of GK from the glucokinase regulatory protein, and the subsequent relocalization of GK from the nucleus to the cytoplasm, is impaired (28, 70, 71). This evidence concerns the gene GCK and diabetes mellitus.