A modified insulin regulates insulin secretion dynamically: animal experiments

https://www.nature.com/articles/s41551-023-01138-7

https://spc.jst.go.jp/news/231202/topic_3_05.html

A team led by Professor Gu Sheng from Zhejiang University School of Pharmacy and Jinhua Research Institute has developed a long-acting insulin formulation. The drug senses fluctuations in blood glucose levels and dynamically regulates insulin secretion to control blood glucose levels for a long period of time.

Beta cells in the human body can sense the concentration of glucose and regulate the rate of glucose metabolism in the body by controlling the amount of insulin secreted. Diabetics, however, may lack beta cells or be insensitive to insulin, making it difficult for them to maintain normal blood glucose levels.

The new complex developed by the team is made by tightly coupling gluconic acid-modified recombinant human insulin with phenylboronic acid-modified polylysine. When injected subcutaneously, the new complex acts like an insulin “reservoir,” storing insulin under the skin for a long period of time and rapidly secreting it when blood glucose levels rise. This new complex changes the difficulties of conventional insulin preparations, which are prone to leakage and difficult to treat over a long period of time. Under normal blood glucose conditions, it can slowly release small amounts of insulin, maintaining basic blood glucose stability. On the other hand, as blood glucose levels rise, glucose competitively binds to the “suckers” in the complex, rapidly releasing insulin and bringing blood glucose levels back into the normal range.

In previous experiments, a single dose of the drug was sufficient to maintain normal blood glucose levels for more than a week in a 30-kilogram model pig with type 1 diabetes, and it did not produce hypoglycemic symptoms.

A modified insulin regulates insulin secretion dynamically: animal experiments
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