相关实验视频
Updated: Jun 9, 2025

12:08
Improving IV Insulin Administration in a Community Hospital
Published on: June 11, 2012
18.8K
胰岛素稳定设计可提高治疗效率和可访问性
Yanxian Zhang1, Maxwell Jack Austin1,2, Danny Hung-Chieh Chou1
1Division of Endocrinology and Diabetes, Department of Pediatrics, School of Medicine, Stanford University, Stanford, California 94305, United States.
Accounts of chemical research
|October 28, 2024
概括
研究人员开发了稳定的胰岛素类似物和配方策略,以改善胰岛素治疗,解决诸如冷链要求和低于最佳患者结果等挑战,以更好地管理糖尿病.
科学领域:
- 蛋白质工程和制药配方制造
- 生物化学和药物输送
背景情况:
- 自1921年以来对糖尿病的胰岛素治疗至关重要,由于蛋白质的不稳定性而面临挑战,需要严格的冷链管理.
- 目前的胰岛素配方具有苛刻的治疗方案和低于最佳的结果,需要更安全,更易于使用的替代品.
- 现有的胰岛素稳定方法有限,导致需要与先进疗法兼容的新方法.
研究的目的:
- 设计新的,稳定的胰岛素类似物,并探索配方设计策略,以提高水溶液中的胰岛素稳定性.
- 为了解决传统胰岛素稳定方法的局限性,并探索替代的,不那么侵袭的注射途径.
- 从工业和研究的角度提供对胰岛素稳定性的全面概述.
主要方法:
- 开发了一种具有增强聚合稳定性和效力的四硫化胰岛素模拟剂.
- 创建了结构缩小的,完全活跃的胰岛素类似物,以促进单质状态和快速吸收.
- 研究了用可生物降解的多辅助剂进行黄[7]uril (CB[7]) 辅助稳定,并探索了N端替代以进行pH依赖稳定.
主要成果:
- 成功设计了一种新型的四硫化物胰岛素模拟物,证明了其高稳定性和功效.
- 开发了小型化的胰岛素类似物,这些类似物仍然是单质的,为超快速起作用的胰岛素铺平了道路.
- 确定了CB[7]辅助稳定和pH依赖稳定的策略,扩大了胰岛素配方的可能性.
结论:
- 新型蛋白质工程和配方策略可以显著提高胰岛素稳定性和治疗潜力.
- 这些进展为更稳定,更易于使用的胰岛素疗法提供了途径,可能减少自我管理负担.
- 蛋白质工程,配方设计和药物输送方面的持续跨学科努力对于下一代胰岛素疗法至关重要.
相关概念视频
Insulin Formulations: Types and Delivery
171
Insulin preparations are categorized by their duration of action into short-acting and long-acting types. Two strategies are used to modify insulin's absorption and pharmacokinetic profile: slowing the absorption post-subcutaneous injection, or altering human insulin's amino acid sequence or protein structure. These changes retain the insulin's ability to bind to the insulin receptor, but alter its behavior in solution or after injection.
Short-acting insulins are divided into...
Short-acting insulins are divided into...
171
Insulin: Dosing Regimen and Adverse Effects
148
Insulin-replacement therapy usually includes both long-acting insulin (basal) and short-acting insulin (to cater to postprandial needs). In a diverse group of type 1 diabetes patients, the average daily insulin dose is typically 0.5-0.7 units/kg body weight. However, obese patients and pubertal adolescents may need more due to insulin resistance.
The basal dose constitutes about 40%-50% of the total daily dose, with the rest as premeal insulin. The mealtime insulin dose should mirror...
The basal dose constitutes about 40%-50% of the total daily dose, with the rest as premeal insulin. The mealtime insulin dose should mirror...
148
Oral Hypoglycemic Agents: Glinides
142
Repaglinide (Prandin) and Nateglinide (Starlix), known as glinides, are oral insulin secretagogues that stimulate insulin release from pancreatic β cells by closing the ATP-sensitive potassium channels (KATP channel). Repaglinide controls insulin release from pancreatic β cells by managing potassium efflux. It shares two binding sites with sulfonylureas and also has a unique site, indicating overlapping mechanisms of action. With a rapid onset and a 4-7 hour duration, it effectively...
142
Glucagon-like Receptor Agonists
301
Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
301
Insulin: Biosynthesis, Chemistry, and Preparation
360
The endoplasmic reticulum (ER) of pancreatic β-cells synthesizes preproinsulin, which consists of a signal peptide, A and B chains, and a C-peptide. Preproinsulin is then cleaved and folded into proinsulin, which translocates to the Golgi apparatus for sorting and packaging into secretory granules. In these granules, enzymatic clipping generates insulin and C-peptide.
Damage or functional impairment of β-cells inhibits insulin production, leading to diabetes. Diabetes treatment...
Damage or functional impairment of β-cells inhibits insulin production, leading to diabetes. Diabetes treatment...
360
Oral Hypoglycemic Agents: Biguanides and Glitazones
176
Biguanides, particularly metformin (Glucophage), are insulin sensitizers that enhance glucose uptake, thereby reducing insulin resistance. Unlike sulfonylureas, metformin doesn't prompt insulin secretion, which helps to curb hypoglycemia risk. Metformin is beneficial in treating conditions like polycystic ovary syndrome due to its insulin-resistance reduction capability. The drug's primary action involves curtailing hepatic gluconeogenesis, a significant contributor to high blood...
176

