The fruit fly Drosophila melanogaster is increasingly utilized as an alternative to costly rodent models to study human diseases. Fly models exist for a wide variety of human conditions, such as Alzheimer's and Parkinson’s Disease, or cardiac function. Advantages of the fly system are its rapid generation time and its low cost. However, the greatest strength of the fly system are the powerful genetic tools that allow for rapid dissection of molecular disease mechanisms. Here, we describe the diet-dependent development of metabolic phenotypes in adult fruit flies. Depending on the specific type of nutrient, as well as its relative quantity in the diet, flies show weight gain and changes in the levels of storage macromolecules. Furthermore, the activity of insulin-signaling in the major metabolic organ of the fly, the fat body, decreases upon overfeeding. This decrease in insulin-signaling activity in overfed flies is moreover observed when flies are challenged with an acute food stimulus, suggesting that overfeeding leads to insulin resistance. Similar changes were observed in aging flies, with the development of the insulin resistance-like phenotype beginning at early middle ages. Taken together, these data demonstrate that imbalanced diet disrupts metabolic homeostasis in adult D. melanogaster and promotes insulin-resistant phenotypes. Therefore, the fly system may be a useful alternative tool in the investigation of molecular mechanisms of insulin resistance and the development of pharmacologic treatment options.

We have successfully transfected mouse genomic DNA containing a mutant putative K+ channel gene into murine LMTK- cells. Incorporation of the mutant gene allowed primary transformants to express the mutant cell phenotype of growth at a subthreshold K+ concentration and, furthermore, caused these primary transformants to display the same characteristics of growth and unidirectional K+ flux as the mutant cell line, LTK-1, from which the genomic DNA was derived. A cosmid genomic library was formed from LTK-1 mutant DNA and shown by transfection experiments to contain at least one unique cosmid clone containing a functional copy of the mutant putative K+ channel gene.