Diabetes mellitus results in complex metabolic and structural alterations, and the molecular mechanisms for many of these changes are currently not completely understood. Some mechanisms of posttranslational modifications (eg, phosphorylation) of proteins have already been related to the metabolic anomalies characteristic of diabetes. These have been the subject of other reviews and, therefore, will not be considered here. In this overview, I will discuss how insulin deficiency has been shown to mediate the amounts of specific proteins and the corresponding mRNAs which code for them. Within this context, it is the insulin modulation of an individual protein’s synthesis rate, rather than degradation, which will be considered here. The action of insulin on the level of specific mRNAs may result directly from receptor-mediated events, or indirectly via alterations in metabolism. An example would be the welldescribed indirect action of insulin to alter glucose metabolism, which has recently been shown to regulate the expression of specific hepatic mRNAs such as pyruvate kinase mRNA. The effect of carbohydrate metabolism on specific gene regulation, as well as other examples of the effect of insulin on specific mRNAs and protein, will be discussed in further detail. Additionally, insulin modulates the level of total protein synthesis; this will be discussed only briefly. Decreased levels of insulin as they occur in Type I diabetes mellitus lead to a marketed reduction in total protein synthesis and in addition, affects the level of several specific proteins. Changes in these specific proteins are out-of-line with the general decrease in protein synthesis and are accompanied by corresponding alterations in