DEVELOPMENT OF CONCENTRATED, STABLE ULTRA FAST-ACTING INSULIN FORMULATION

NIH RePORTER · NIH · R01 · $559,768 · view on reporter.nih.gov ↗

Abstract

For people with diabetes, maintaining optimal blood glucose levels is effective in delaying or even preventing long-term complications. Tremendous efforts have been made in developing fast-acting and long-lasting analogues to provide better glycemic control compared to native insulin. Unfortunately, most people are unable to consistently meet their target glycemic range, and aggressive efforts to reach this goal can cause frequent and potentially life-threatening episodes of hypoglycemia. A key challenge lies in the slow onset and long duration of the currently available fast-acting insulin therapeutics, which restricts the effectiveness of insulin therapy. Efforts to develop new fast-acting insulins have been limited by the involvement of the same residues in both insulin dimerization and receptor binding, which presents the conundrum that mutations that increase speed of availability also negate signaling. Consequently, no new fast-acting insulins have been approved in the past decade. To overcome this fundamental blockage, we are taking an approach that is inspired by recent insights from the study of fish-hunting cone snails that use a specialized venom insulin variant to rapidly induce hypoglycemic shock in their prey. Our preliminary data show that this venomous insulin is monomeric, binds to human insulin receptor, activates the insulin-signaling pathway, and reduces blood sugar levels in mice. These data provide a strong foundation to learn further insights from the fascinating arsenal of venomous insulins. Successful outcome will provide a platform upon which a powerful new class of therapeutics can be developed for the treatment of diabetes.

Key facts

NIH application ID
10161661
Project number
7R01DK120430-03
Recipient
STANFORD UNIVERSITY
Principal Investigator
Danny Hung-Chieh Chou
Activity code
R01
Funding institute
NIH
Fiscal year
2020
Award amount
$559,768
Award type
7
Project period
2018-09-15 → 2022-05-31