Development of Liver-Targeting Insulin
Abstract
This project proposes to develop liver-targeting insulin as next-generation insulin to combat diabetes. Critical Problem to Be Addressed: In a healthy individual, insulin is first delivered to liver, which takes ~50% of all insulin before the rest is delivered to other parts of body. In current insulin therapy for diabetics, more insulin action happens in places such as fat and muscle cells relative to liver cells. This outcome is known to be associated with atherosclerosis, cancer, hypoglycemia, and other adverse metabolic effects. To overcome this limitation, it is proposed to develop new liver-targeting insulin therapies such that more insulin could be delivered to the liver in order to mimic the healthy conditions. Innovation: This project proposes, for the first time, to chemically modify insulin with a liver-targeting ligand. It is expected that the newly designed insulin has the same bioactivity as native insulin but will be preferentially delivered to liver after injection. 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 longstanding pharmacological limitation for diabetics who require insulin self-administration and holds great promise to improve the quality of life for diabetic patients by minimizing the risk of severe hypoglycemia, weight gain, and other detriments that currently accompany exogenous insulin administration.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610139
Entities
People
- Danny Chou
Organizations
- United States Army
- University of Utah