Development of Glucose-Responsive Insulin
Abstract
This project proposes to develop glucose-responsive insulin as next-generation insulin to combat diabetes. Critical Problem to Be Addressed: Millions of people with 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-acting and long-acting insulin analogs have been in the market and provide clinical benefits for diabetic patients, these insulin analogs still cause hypoglycemia, an acute complication that may lead to coma or death. To reduce the risk of hypoglycemia, a glucose-responsive insulin analog 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 diabetes. By introducing glucose-responsive segments to insulin molecules, this project aims to insert a glucose switch to insulin. In low glucose conditions the ?smart insulin? is inactive, while in high glucose conditions the ?smart insulin? is active and triggers peripheral cells to uptake glucose from blood to maintain normal blood glucose levels. Innovation: Currently, there is no Food and Drug Administration-approved insulin therapeutic that is responsive to circulating glucose levels. This project proposes, for the first time, to control the in vivo action of insulin through manipulations of protein solubility in response to blood glucose levels. This promising strategy may lead to major breakthroughs and represents a truly novel paradigm shift in the treatment of diabetes. Applicability and Research Impacts: This proposal is primarily aimed at demonstrating feasibility within 2 years in a preclinical setting. If successful, an additional 2-3 years of optimization, preclinical safety, and non-rodent studies (e.g., dog and pig) could lead to a clinical candidate. This innovative approach has the potential to solve a long-standing therapeutic limitation for diabetics who require insulin self-administration and holds a great promise to improve the quality of life for diabetic patients by minimizing the risk of severe hypoglycemia that currently accompanies exogenous insulin administration.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 05, 2019
- Source ID
- W81XWH1910061
Entities
People
- Danny Chou
Organizations
- United States Army
- University of Utah