Insulin short-term control of rat liver alpha 2-microglobulin gene transcription

By differential screening of a rat liver cDNA library, we have isolated several cDNA clones whose respective mRNAs are decreased in liver from diabetic rats. One such clone corresponding by DNA sequence to alpha 2-microglobulin mRNA has been used in the present study. As it was described previously a reduction (10 times) of alpha 2-microglobulin mRNA levels is observed in liver from diabetic animals. Insulin both in vivo and in isolated hepatocytes from diabetic rats is able to increase the level of alpha 2-microglobulin mRNA within 15 min. This fast effect of insulin is dose-dependent (half-maximal dose at 10(-10) M), indicating that it is likely to be mediated through the insulin receptor. Insulin induction is primarily due to an increase in the rate of transcription of the gene as judged by nuclear run-on transcription experiments and by its complete prevention with actinomycin D. These data indicate that alpha 2-microglobulin gene is a fast insulin-responsive gene and constitutes a good model gene to study the possible regulatory sequences involved in the control of gene transcription by insulin.