Objective
This project aims to develop glucose-responsive insulin derivatives that response to blood glucose levels. Such insulin could self-regulate its bioactivity in order to maintain blood glucose levels and reduce the risks of hypoglycemia.
Background Rationale
People with type 1 diabetes rely on insulin injection to maintain normal glucose levels; however, they still suffer from multiple daily injections and poor blood glucose control. Although both fast-acing and long-acting insulin analogues have been in the market and provide clinical benefits for diabetic patients, these insulin analogues still cause hypoglycemia, an acute complication that may lead to coma or death. To reduce the risk of hypoglycemia, a glucose-responsive insulin (GRI) derivative is needed that would be active when blood glucose levels are high, yet become inactivated when blood glucose levels start to decline. Such a “smart insulin” will eliminate the barrier of hypoglycemia for people with T1D and improve the qualities of their daily lives. By introducing glucose-responsive segments to insulin molecules, this project aims to insert a glucose switch to insulin. In low glucose conditions this “smart insulin” is inactive, while in high glucose concentration this “smart insulin” is active and triggers peripheral cells to uptake glucose from blood to maintain normal glucose levels.
Description of Project
People with type 1 diabetes rely on insulin injection to maintain normal glucose levels; however, they still suffer from multiple daily injections and poor blood glucose control. To reduce the risk of hypoglycemia, a glucose-responsive insulin is needed that is active when blood glucose levels are high, yet is inactivated when blood glucose levels start to decline. Such a “smart insulin” will eliminate the barrier of hypoglycemia for people with type 1 diabetes. By introducing glucose-responsive segments to insulin molecules, this project aims to develop an insulin molecule that can self-regulate its bioactivity in vivo. Such insulin may therefore provide enhanced safety feature and lead to tighter glycemic control.
Anticipated Outcome
We aim to identify insulin derivatives with glucose responsiveness confirmed in animal diabetes models. Such insulin will be candidates for future clinical translations.
Relevance to T1D
This project aims to develop insulin that will ease the burden for people with T1D. Specifically, this insulin may provide improved glycemic control, reduced hypoglycemic risk and better patient convenience.