Lost in Translation

There are few methodologies that have done more to advance our understanding of insulin action in humans and animals than the hyperinsulinemic-euglycemic clamp (henceforth referred to as the insulin clamp or clamp). The clamp was first developed for use in humans by DeFronzo, Tobin, and Andres at Johns Hopkins in 1979 (1). This technique was transferred to the rat in 1983 (2,3) and the mouse in the early 1990s (4,5). The insulin clamp is often combined with isotopic methods so that the investigator cannot only determine a total whole-body insulin action but also how specific tissues and metabolic pathways are affected. The adaptation of the insulin clamp for use in the mouse has been critical to the characterization of the still growing number of mouse models with modifications to the genes involved in the regulation of glucose and energy homeostasis. Despite the importance of this tool, a significant deficiency has evolved in the process of translating the clamp from humans to mice. The first articles reporting insulin clamps in the mouse conscientiously presented methods and results (4,5). However, since these first studies in the mouse, the care and conventions of the human clamp literature that immediately followed its development have largely been traded for no, minimal, or inaccurate description of methods and inadequate presentation of results. The reader is provided with too little information to independently interpret the results of an article. Instead, the reader is solely dependent on the conclusion to which he or she is directed by the authors. The perception that standards in the human and rat literature have lowered in recent years was brought to our attention during the preparation of this article. Here, we focus on the mouse literature. Of course, sound reporting of clamp methods and results applies …