治疗Ⅱ型糖尿病的GLP-1受体激动剂及其高分子递送系统的研究进展.

庄亚平; 杨孝伟; 俞麟; 丁建东

Diabetes is a kind of metabolic disorders disease of aberrant glucose homeostasis that is characterized by elevated blood glucose levels.TypeII diabetes accounts for over 90% of cases globally.There are many different classes of antidiabetes therapies used in clinic,and recently incretin-based therapy has drawn increasing attention.Glucagon-like peptide 1(GLP-1),a incretin hormone produced in the L cells of the intestines,can act on pancreatic islet cells,promote transcription of insulin gene,and augment biosynthesis and secretion of insulin in a glucose-dependent manner without significant risks for hypoglycemia.Additional effects of GLP-1 include inhibitingβ-cell apoptosis,delaying gastric emptying and increasing appetite.However,GLP-1 is easily degraded by dipeptidyl peptidase IV(DPP-4)within2—3 min in the circulation,which significantly limits its therapeutic application.Therefore,a series of strategies including exchanging amino acids to restrain the degradation of DPP-IV,attachment of fatty acid side chains or covalent association with large molecules such as albumin or IgG to extend the duration of action of GLP-1 have been utilized to develop various GLP-1 receptor agonists.These GLP-1 receptor agonists can be classified as either short-acting compounds or as long-acting ones.The short-acting GLP-1 receptors agonists,such as exenatide and lixisenatide,can activate the GLP-1 receptor short-termly,while the long-acting ones,such as liraglutide,albiglutide,dulaglutide and semaglutide,can provide long-lived receptor activation. Meanwhile, multifarious delivery systems of GLP-1 receptor agonists using microspheres,hydrogels,implanted devices or nanoparticles as carriers have also been exploited to provide prolonged in vivo actions,reduce administration frequency and increase patient compliance.This review focuses on the progress of GLP-1 receptor agonists approved by U.S.Food and Drug Administration and their delivery systems,such as injectable thermogel systems containing GLP-1 receptor agonists,for the treatment of typeⅡ diabetes.

CD26 antigen; GLUCAGON-like peptide-1 agonists; BLOOD sugar; ISLANDS of Langerhans; GASTRIC emptying; PEPTIDE hormones; INSULIN; ALBUMINS

Journal of Functional Polymers, 2019, Vol 32, Issue 2, p126

1008-9357

Academic Journal

10.14133/j.cnki.1008-9357.20180810001