An orally available hypoglycaemic peptide taken up by caveolae transcytosis displays improved hypoglycaemic effects and body weight control in db/db mice
| العنوان: | An orally available hypoglycaemic peptide taken up by caveolae transcytosis displays improved hypoglycaemic effects and body weight control in db/db mice |
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| المؤلفون: | Peng Qian, Wenbing Yao, Weisheng Lu, Xiangdong Gao, Ying Li, Yongkang Wang, Hong Tian, Yang Ge, Sai Wenbo |
| المصدر: | Br J Pharmacol |
| بيانات النشر: | Wiley, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Blood Glucose, 0301 basic medicine, Agonist, medicine.drug_class, Mice, Inbred Strains, Pharmacology, Caveolae, Glucagon-Like Peptide-1 Receptor, Diabetes Mellitus, Experimental, Mice, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, Glucagon-Like Peptide 1, Oral administration, Diabetes mellitus, medicine, Animals, Humans, Hypoglycemic Agents, Insulin, Rats, Wistar, Receptor, business.industry, Body Weight, medicine.disease, Research Papers, Glucagon-like peptide-1, Rats, Bioavailability, 030104 developmental biology, Diabetes Mellitus, Type 2, Transcytosis, Caco-2 Cells, Peptides, business, 030217 neurology & neurosurgery |
| الوصف: | Background and purpose Type 2 diabetes is one of the most severe chronic diseases and is an increasingly important public health problem worldwide. Several agonists of the glucagon-like peptide-1 (GLP-1) receptor have been developed to treat Type 2 diabetes but most of them are administered by injection. This mode of administration seriously reduces patient compliance and increases the risk of infection. Here, we describe the actions of a novel, orally available, GLP-1 receptor agonist - oral hypoglycaemic peptide 2 (OHP2) - derived from exendin-4 by replacing amino acids. We have also investigated its pharmacokinetic profiles, therapeutic effects and absorption mechanism. Experimental approach Healthy Wistar rats were used for pharmacokinetic analyses. In diabetic db/db mice. OHP2 was given for 8 weeks to evaluate its effects on hyperglycaemia, dyslipidaemia, basal metabolism and tissue injury. Possible endocytosis and transcytosis mechanisms of OHP2 uptake were explored in Caco-2 cell monolayers. Key results In rats, the absolute bioavailability of orally administered OHP2 was 20-fold greater than that of orally administered exendin-4. In db/db mice, OHP2 dose-dependently exhibits good potential in glucose-lowering and weight loss after oral administration. OHP2 also alleviated hyperlipidaemia, ameliorated energy metabolism and promoted tissue repair in diabetic mice. Furthermore, uptake of OHP2 by Caco-2 cells was dependent on caveolae-mediated transcytosis rather than endocytosis mediated by GLP-1 receptors. Conclusions and implications OHP2 is a potential, orally bioavailable, candidate drug for the treatment of Type 2 diabetes. Its transcytosis mechanism of uptake could help in the development of absorption enhancers of OHP2. |
| تدمد: | 1476-5381 0007-1188 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1c70eef09d0db34d6a64857e11e0b976Test https://doi.org/10.1111/bph.15069Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....1c70eef09d0db34d6a64857e11e0b976 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14765381 00071188 |
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