Towards the Development of a Real‐time Insulin Biosensor

Abstract

Disease management for Type 1 Diabetes (T1D) patients can be challenging, and more than two-thirds of the diabetic population in the United States fails to maintain optimal blood glucose levels. The artificial pancreas (AP), automates disease management by automatically delivering insulin with dosage adjusted in real-time as a response to blood glucose levels. However, despite automation using advanced control algorithms, patients reliant on the AP risk hyper and hypoglycemia, which can result in fatality or other less serious complications. Such mis-dosing can result from discrepancies between the administered and the circulating insulin levels. As such, a direct continuous monitoring of circulating insulin could tighten glucose regulation while improving safety and patient response to treatment. Thus, we aim to develop a real-time insulin biosensor for APs using nature's own insulin sensor, the insulin receptor (InR). We plan to engineer our biosensor modeled upon the InR ectodomain using phage-displayed libraries with 109 different InR variants and iterative rounds of selections. FRET and polarization assays will be used to assess InR conformational change, binding kinetics of insulin to InR variants, and device sensitivity. Support or Funding Information Juvenile Diabetes Research Foundation, The Helmsley Charitable Trust Insulin binding (kon) and release (koff) kinetics determine sensitivity of insulin monitoring over a dynamic range of concentrations. Conformational changes of the native InR are used to develop a FRET-based optical detection system for insulin binding using fusion proteins covalently attached to fluorophores. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.