Helical‐Like Assembly of Nateglinide as Coating for Oral Delivery of Insulin and Their Synergistic Prevention of Diabetes Mellitus
Abstract Oral delivery of antidiabetic active components promises to free millions of people from daily suffering who require routine injections. However, oral insulin (Ins) and other short‐acting compounds such as nateglinide (NG) in harsh gastrointestinal tract still face great challenging, includ...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-10-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202301879 |
| _version_ | 1797657815833116672 |
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| author | Yanfei Li Lihang Chen Yu Xu Sihui Li Huijia Yan Tao Chen Ziqi Hua Di Wu Runan Zhao Jiangning Hu |
| author_facet | Yanfei Li Lihang Chen Yu Xu Sihui Li Huijia Yan Tao Chen Ziqi Hua Di Wu Runan Zhao Jiangning Hu |
| author_sort | Yanfei Li |
| collection | DOAJ |
| description | Abstract Oral delivery of antidiabetic active components promises to free millions of people from daily suffering who require routine injections. However, oral insulin (Ins) and other short‐acting compounds such as nateglinide (NG) in harsh gastrointestinal tract still face great challenging, including low bioavailability, and rapid elimination. In this study, inspired by the self‐assembly of phenylalanine‐based peptides in nature, it is showed that NG a small phenylalanine derivative, assembles into left‐handed helical nanofibers in the presence of Ca2+. These helical NG nanofibers functioned as a coating layer on the surface of Ca2+‐linked alginate (Alg) microgels for the effective encapsulation of Ins. As expected, the sustained release and prolonged circulation of Ins and NG from the Ins‐loading Alg/NG microgels (Ins@Alg/NG) in the intestinal tract synergistically maintain a relatively normal blood glucose level in streptozotocin‐induced diabetic mice after oral administration of Ins@Alg/NG. This further confirms that Ins@Alg/NG ameliorated Ins resistance mainly through activating Insreceptor substrate 1 (IRS1), protein kinase B (AKT), and AMP‐activated protein kinase (AMPK), as well as by repressing glycogen synthase kinase‐3β (GSK‐3β). The strategy of using the assembly of NG as a coating achieves the oral delivery of insulin and showcases a potential for the treatment of diabetes. |
| first_indexed | 2024-03-11T17:51:04Z |
| format | Article |
| id | doaj.art-7dd0184c52bf446eabecbca66b07d9c3 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-03-11T17:51:04Z |
| publishDate | 2023-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-7dd0184c52bf446eabecbca66b07d9c32023-10-18T06:07:54ZengWileyAdvanced Science2198-38442023-10-011029n/an/a10.1002/advs.202301879Helical‐Like Assembly of Nateglinide as Coating for Oral Delivery of Insulin and Their Synergistic Prevention of Diabetes MellitusYanfei Li0Lihang Chen1Yu Xu2Sihui Li3Huijia Yan4Tao Chen5Ziqi Hua6Di Wu7Runan Zhao8Jiangning Hu9SKL of Marine Food Processing & Safety Control National Engineering Research Center of Seafood Collaborative Innovation Center of Seafood Deep Processing School of Food Science and Technology Dalian Polytechnic University Dalian 116034 ChinaSKL of Marine Food Processing & Safety Control National Engineering Research Center of Seafood Collaborative Innovation Center of Seafood Deep Processing School of Food Science and Technology Dalian Polytechnic University Dalian 116034 ChinaSKL of Marine Food Processing & Safety Control National Engineering Research Center of Seafood Collaborative Innovation Center of Seafood Deep Processing School of Food Science and Technology Dalian Polytechnic University Dalian 116034 ChinaSKL of Marine Food Processing & Safety Control National Engineering Research Center of Seafood Collaborative Innovation Center of Seafood Deep Processing School of Food Science and Technology Dalian Polytechnic University Dalian 116034 ChinaSKL of Marine Food Processing & Safety Control National Engineering Research Center of Seafood Collaborative Innovation Center of Seafood Deep Processing School of Food Science and Technology Dalian Polytechnic University Dalian 116034 ChinaSKL of Marine Food Processing & Safety Control National Engineering Research Center of Seafood Collaborative Innovation Center of Seafood Deep Processing School of Food Science and Technology Dalian Polytechnic University Dalian 116034 ChinaSKL of Marine Food Processing & Safety Control National Engineering Research Center of Seafood Collaborative Innovation Center of Seafood Deep Processing School of Food Science and Technology Dalian Polytechnic University Dalian 116034 ChinaSKL of Marine Food Processing & Safety Control National Engineering Research Center of Seafood Collaborative Innovation Center of Seafood Deep Processing School of Food Science and Technology Dalian Polytechnic University Dalian 116034 ChinaSKL of Marine Food Processing & Safety Control National Engineering Research Center of Seafood Collaborative Innovation Center of Seafood Deep Processing School of Food Science and Technology Dalian Polytechnic University Dalian 116034 ChinaSKL of Marine Food Processing & Safety Control National Engineering Research Center of Seafood Collaborative Innovation Center of Seafood Deep Processing School of Food Science and Technology Dalian Polytechnic University Dalian 116034 ChinaAbstract Oral delivery of antidiabetic active components promises to free millions of people from daily suffering who require routine injections. However, oral insulin (Ins) and other short‐acting compounds such as nateglinide (NG) in harsh gastrointestinal tract still face great challenging, including low bioavailability, and rapid elimination. In this study, inspired by the self‐assembly of phenylalanine‐based peptides in nature, it is showed that NG a small phenylalanine derivative, assembles into left‐handed helical nanofibers in the presence of Ca2+. These helical NG nanofibers functioned as a coating layer on the surface of Ca2+‐linked alginate (Alg) microgels for the effective encapsulation of Ins. As expected, the sustained release and prolonged circulation of Ins and NG from the Ins‐loading Alg/NG microgels (Ins@Alg/NG) in the intestinal tract synergistically maintain a relatively normal blood glucose level in streptozotocin‐induced diabetic mice after oral administration of Ins@Alg/NG. This further confirms that Ins@Alg/NG ameliorated Ins resistance mainly through activating Insreceptor substrate 1 (IRS1), protein kinase B (AKT), and AMP‐activated protein kinase (AMPK), as well as by repressing glycogen synthase kinase‐3β (GSK‐3β). The strategy of using the assembly of NG as a coating achieves the oral delivery of insulin and showcases a potential for the treatment of diabetes.https://doi.org/10.1002/advs.202301879diabeteshelical nanofibersnateglinideoral deliveryself‐assembly |
| spellingShingle | Yanfei Li Lihang Chen Yu Xu Sihui Li Huijia Yan Tao Chen Ziqi Hua Di Wu Runan Zhao Jiangning Hu Helical‐Like Assembly of Nateglinide as Coating for Oral Delivery of Insulin and Their Synergistic Prevention of Diabetes Mellitus Advanced Science diabetes helical nanofibers nateglinide oral delivery self‐assembly |
| title | Helical‐Like Assembly of Nateglinide as Coating for Oral Delivery of Insulin and Their Synergistic Prevention of Diabetes Mellitus |
| title_full | Helical‐Like Assembly of Nateglinide as Coating for Oral Delivery of Insulin and Their Synergistic Prevention of Diabetes Mellitus |
| title_fullStr | Helical‐Like Assembly of Nateglinide as Coating for Oral Delivery of Insulin and Their Synergistic Prevention of Diabetes Mellitus |
| title_full_unstemmed | Helical‐Like Assembly of Nateglinide as Coating for Oral Delivery of Insulin and Their Synergistic Prevention of Diabetes Mellitus |
| title_short | Helical‐Like Assembly of Nateglinide as Coating for Oral Delivery of Insulin and Their Synergistic Prevention of Diabetes Mellitus |
| title_sort | helical like assembly of nateglinide as coating for oral delivery of insulin and their synergistic prevention of diabetes mellitus |
| topic | diabetes helical nanofibers nateglinide oral delivery self‐assembly |
| url | https://doi.org/10.1002/advs.202301879 |
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