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X-ray crystallography reveals insulin lisargine structure and mechanisms of glucose regulation
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X-ray crystallography reveals insulin lisargine structure and mechanisms of glucose regulation
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Journal Article
X-ray crystallography reveals insulin lisargine structure and mechanisms of glucose regulation
2025
Overview
The development of effective and safe insulin analogs remains pivotal in advancing diabetes management. This study addresses the limitations of existing insulin therapies by introducing insulin lisargine, a novel long-acting insulin analog that resolves impurity formation associated with trypsin cleavage in glargine insulin. Insulin lisargine is characterized by glycine substitution at A21 and the addition of lysine and arginine at B31 and B32, respectively. High-performance liquid chromatography (HPLC) and mass spectrometry confirmed its high purity and precise molecular weight. X-ray crystallography at 2.0 Å resolution revealed structural features closely resembling human insulin, crucial for optimizing drug formulations and understanding receptor interactions.In vivo experiments demonstrated that insulin lisargine exhibits superior glucose-lowering effects compared to glargine insulin (Lantus). At a dosage of 1.5 IU/kg, lisargine achieved glucose-lowering effects equivalent to glargine in normal rats. However, at 5 IU/kg, it significantly outperformed glargine in type 1 diabetic rats. Long-term safety assessments revealed a comparable safety profile between lisargine and glargine, with no significant toxicity observed. These findings position insulin lisargine as a promising candidate for diabetes management, offering enhanced blood glucose control, improved production efficiency, and reliable safety. The study’s findings provide a foundation for the development of more effective insulin analogs, addressing critical needs in diabetes therapy.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 631/1647
/ 631/337
/ 631/61
/ Animals
/ Blood Glucose - drug effects
/ Crystals
/ Diabetes
/ Diabetes Mellitus, Experimental - drug therapy
/ Diabetes Mellitus, Type 1 - drug therapy
/ Glucose
/ High-performance liquid chromatography
/ Humanities and Social Sciences
/ Humans
/ Hypoglycemic Agents - chemistry
/ Hypoglycemic Agents - pharmacology
/ Insulin
/ Insulin Glargine - chemistry
/ Insulin Glargine - pharmacology
/ Insulin Lispro - pharmacology
/ Male
/ Rats
/ Safety
/ Science
/ Software
/ Toxicity
/ Trypsin
