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Homogeneous Time-resolved Förster Resonance Energy Transfer-based Assay for Detection of Insulin Secretion
Published on: May 10, 2018
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Glucose-sensitive insulin with attenuation of hypoglycaemia
Thomas Hoeg-Jensen1, Thomas Kruse1, Christian L Brand2
1Global Research Technologies, Novo Nordisk, Bagsværd, Denmark.
Nature
|October 16, 2024
Summary
Researchers developed NNC2215, a novel glucose-sensitive insulin, to automatically adjust its activity based on blood glucose levels. This innovation aims to improve diabetes management by reducing the risk of hypoglycemia while maintaining glycemic control.
Area of Science:
- Biochemistry
- Endocrinology
- Pharmaceutical Science
Background:
- Insulin therapy for diabetes poses a significant risk of hypoglycemia due to difficulties in dose adjustment.
- Achieving optimal glycemic control requires precise insulin delivery that adapts to fluctuating blood glucose levels.
- The development of glucose-sensitive insulin is a long-standing goal to mitigate hypoglycemia risks.
Purpose of the Study:
- To design and characterize NNC2215, a novel insulin conjugate with reversible glucose-sensitive bioactivity.
- To evaluate the in vitro and in vivo performance of NNC2215 for diabetes management.
- To demonstrate the potential of NNC2215 in achieving better glycemic control and reducing hypoglycemia.
Main Methods:
- Engineered NNC2215 by conjugating a glucose-binding macrocycle and a glucoside to insulin.
- Assessed changes in NNC2215 insulin receptor affinity across varying glucose concentrations (3-20 mM).
- Conducted in vivo animal studies to evaluate the glucose-sensitive bioactivity and safety profile of NNC2215.
Main Results:
- NNC2215 exhibited reversible bioactivity responsive to a clinically relevant glucose range.
- Insulin receptor affinity for NNC2215 increased 3.2-fold with rising glucose concentrations.
- In vivo studies demonstrated NNC2215's protective effect against hypoglycemia and partial control of glucose excursions.
Conclusions:
- NNC2215 represents a significant advancement in glucose-sensitive insulin development.
- The engineered insulin conjugate shows promise for improved diabetes therapy by auto-adjusting bioactivity.
- NNC2215 offers a potential strategy to enhance glycemic control while minimizing the risk of hypoglycemia.
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