Diabetes affects similarly the catalytic subunit and putative glucose-6-phosphate translocase of glucose-6-phosphatase

The effect of streptozocin diabetes on the expression of the catalytic subu nit (p36) and the putative glucose-6-phosphate translocase (p46) of the glu cose-6-phosphatase system (G6Pase) was investigated in rats. In addition to the documented effect of diabetes to increase p36 mRNA and protein in the liver and kidney, a similar to 2-fold increase in the mRNA abundance of p46 was found in liver, kidney, and intestine, and a similar increase was foun d in the p46 protein level in liver. In HepG2 cells, glucose caused a dose- dependent (1-25 mar) increase (up to B-fold) in p36 and p46 mRNA and a less er increase in p46 protein, whereas insulin (1 mu M) suppressed p36 mRNA, r educed p46 mRNA level by half, and decreased p46 protein by about 33%. Cycl ic AMP (100 mu M) increased p36 and p46 mRNA by >2- and 1.5-fold, respectiv ely, but not p46 protein. These data suggest that insulin deficiency and hy perglycemia might each be responsible for up-regulation of G6Pase in diabet es. It is concluded that enhanced hepatic glucose output in insulin-depende nt diabetes probably involves dysregulation of both the catalytic subunit a nd the putative glucose-6-phosphate translocase of the liver G6Pase system.