Biologically Inspired and Chemically Derived Methods for Glucose-Responsive Insulin Therapy.

The controlled delivery of therapeutics in a manner responsive to physiological indicators has promise in realizing new therapeutic approaches to combat disease. This approach is especially relevant in the context of diabetes. Natural fluctuations in blood glucose seen in the healthy state, complete with peaks and troughs, are poorly regulated as a result of detrimental production or ineffective signaling of the insulin hormone. While several manifestations of diabetes are treated with regularly administered exogenous insulin, the present standard of care results in suboptimal glycemic management that poorly recreates natural hormone control, leading to long-term instability and a significantly increased risk for secondary health complications. New synthetic technologies that make insulin available only when needed, and at the exact dose required, have been explored under the broad vision of realizing a "fully synthetic pancreas." Yet, many challenges remain to realizing a technology that is appropriately responsive, safe, and well integrated into a manageable routine. Herein, many of the approaches explored thus far to sense physiological blood glucose and elicit response through the release of therapeutic insulin are summarized. The approaches point to a new, autonomous approach to managing diabetes with biomimetic therapy.