The complex nature of metabolic diseases often relies on the use of animal models for drug development and testing. However, recent advances in disease-relevant cellular models and cell-based assays offer opportunity for more rapid and cost-effective studies. Here, we describe the development and implementation of luminescent cell-based assays to study insulin and glucagon secretion and measure their control of diverse metabolic pathways. To measure insulin and glucagon secretion, we developed no-wash immunoassays using luciferase complementation technology. Immunoassays have sensitive detection from 10pM to 8nM (insulin) and 0.5pM to 1nM (glucagon) . They have broad utility for measuring hormone secretion from cells and islets. Furthermore, they can be scaled to 384-well plates, which enables the rapid, cost-effective measurement of large numbers of samples, such as from perifusion or high-throughput screening experiments. To investigate hormone action on glucose and lipid metabolism, we developed a core luminescent technology that couples specific metabolite dehydrogenases to the production of NAD (P) H and the generation of light. Assays can be used in cellular models, reducing the need for animal studies. Luminescent glucose uptake assay was validated as insulin potency assay: insulin-stimulated glucose uptake in 3T3-L1 MBX adipocytes was measured within the expected pharmacology and a 10-fold assay window. The utility of a glucose assay for measuring insulin effect on gluconeogenesis was demonstrated using iPS-derived hepatocytes, and triglyceride assays provided rapid tool for lipogenesis studies in liver microtissues. All assays were scalable and amenable to automation, making them well-suited for high-throughput screening and new drug development.


K.Haupt: None. D.M.Leippe: None. J.Vidugiriene: None.

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