Potential of birds to serve as a pathology-free model of type 2 diabetes, Part 1: Is the apparent absence of the rage gene a factor in the resistance of avian organisms to chronic hyperglycemia?

Diabetes mellitus is a global pandemic that accounts for ever-increasing rates of morbidity and mortality and consumes a growing share of national health care budgets. In spite of concerted efforts, a solution to this problem has not yet been found. One reason for this situation is lack of good animal models. Such models have been used successfully in many areas of biomedical research, but they have proven less than satisfactory in studies on diabetic complications. In this article, we propose to supplement traditional animal models of diabetes that use longitudinal, prospective studies of sick animals (mammals) with retrospective/comparative investigations of healthy animals (birds). Avians are promising models for such studies because they live healthy lives with chronic hyperglycemia that would be fatal to humans. We outline the advantages of the new perspective and show how, by implementing this approach, we observed that birds appear to be missing an important gene linked to diabetic complications. The protein encoded by this gene is a receptor for advanced glycation end products (RAGEs). Although the absence of RAGEs from birds has yet to be confirmed at the protein level, other differences between humans and birds may also be important in accounting for the ability of birds to live with chronic hyperglycemia. Two such additional such characteristics are currently being explored, and it is probable that more will emerge in time. We believe that the proposed perspective may improve the understanding of diabetes mellitus and may help in developing new means for controlling and preventing diabetic complications.