Human lymphocyte messenger RNA activity profiles in type I and type II diabetes: A tool for classification of metabolic disease

We have previously used rat hepatic messenger ribonucleic acid (mRNA) activity profiles to categorize various pathophysiologic states. To test the hypothesis that similar techniques can be used to categorize disease states in humans, we examined the mRNA activity profiles by using in vitro translational assays of Ficoll-Hypaque-separated mononuclear cells obtained from six normal volunteers, six patients with type I diabetes, and five patients with type II diabetes as examples of different disease states. Translated proteins were labeled with sulfur 35-labeled methionine, separated by two-dimensional gel electrophoresis, and quantitated by videodensitometry of autoradiographs derived from the two-dimensional gels. Of approximately 160 quantitated mRNAs, the levels of 12 were found to be altered in one of the diabetic states. The values of nine were changed in patients with type I diabetes and the values of 11 were altered in patients with type II diabetes. Although the values of most mRNAs increased, significant decreases were also observed. Moreover, four spots showed significant differences inr response between the two diabetic states. Discriminant analysis allowed the separation of all three states. Finally, several mRNAs also displayed an age-related correlation. We have demonstrated that unstimulated mononuclear cell mRNAs can be used to study the effects of pathophysiologic states on gene expression in humans. Furthermore, our results support the potential use of this tissue to study the effect of a wide variety of disease states on gene expression.