EFFECT OF ACUTE DIABETES ON RAT HEPATIC GLUCOSE-6-PHOSPHATASE ACTIVITY AND ITS MESSENGER-RNA LEVEL

Glucose-6-phosphatase catalyzes the final step of glucose production b y liver and kidney. Though its strategic position has sparked interest in its regulation, difficulty with isolating a pure, stable enzyme ha s slowed progress. Virtually all previous work examining the physiolog ic regulation of this enzyme has relied on estimates of glucose-6-phos phatase activity in crude microsome preparations. The recent cloning o f human and murine glucose-6-phosphatase cDNAs has now allowed study o f its mRNA expression. We studied the effect of acute, streptozotocin- induced diabetes on hepatic microsomal glucose-6-phosphatase activity and mRNA expression in young (89+/-3 g), juvenile (304+/-4 g) and adul t (512+/-10 g) rats. In control rats, mRNA expression and enzyme activ ity was similar among the three age groups. Streptozotocin-induced dia betes significantly increased the enzyme activities in both intact and triton-treated microsomes in all groups of rats (p<0.001). Glucose-6- phosphatase mRNA expression was increased in the diabetic rats as well (p<0.0001). Blood glucose concentrations correlated significantly wit h glucose-6-phosphatase mRNA level (p<0.005) and both intact (p<0.002) and triton-treated (p<0.001) microsomal glucose-6-phosphatase activit y. Both intact and triton-treated microsomal glucose-6-phosphatase act ivity correlated with mRNA level (p<0.001, for each). We conclude that acute streptozotocin-diabetes increases expression of glucose-6-phosp hatase mRNA and this contributes to the increased glucose-6-phosphatas e activity seen with diabetes mellitus. (C) 1994 Academic Press, Inc.