scholarly journals Polymer-Based Delivery of Glucagon-Like Peptide-1 for the Treatment of Diabetes

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Pyung-Hwan Kim ◽  
Sung Wan Kim
Keyword(s):  
Half Life ◽  
Renal Elimination ◽  
Chemical Conjugation ◽  
Dpp Iv ◽  
Polymeric Delivery ◽  
Treatment Of Diabetes ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Insulinotropic Effect

The incretin hormones, glucagon-like peptide-1 (GLP-1) and its receptor agonist (exendin-4), are well known for glucose homeostasis, insulinotropic effect, and effects on weight loss and food intake. However, due to the rapid degradation of GLP-1 by dipeptidylpeptidase-IV (DPP-IV) enzyme and renal elimination of exendin-4, their clinical applications have been restricted. Although exendin-4 has longer half-life than GLP-1, it still requires frequent injections to maintain efficacy for the treatment of diabetes. In recent decades, various polymeric delivery systems have been developed for the delivery of GLP-1 and exendin-4 genes or peptides for their long-term action and the extra production in ectopic tissues. Herein, we discuss the modification of the expression cassettes and peptides for long-term production and secretion of the native peptides. In addition, the characteristics of nonviral or viral system used for a delivery of a modified GLP-1 or exendin-4 are described. Furthermore, recent efforts to improve the biological half-life of GLP-1 or exendin-4 peptide via chemical conjugation with various smart polymers via chemical conjugation compared with native peptide are discussed.

GLP-1-(9–36) amide reduces blood glucose in anesthetized pigs by a mechanism that does not involve insulin secretion

2002 ◽  
Vol 282 (4) ◽  
pp. E873-E879 ◽  
Author(s):  
Carolyn F. Deacon ◽  
Astrid Plamboeck ◽  
Søren Møller ◽  
Jens J. Holst
Keyword(s):  
Insulin Secretion ◽  
Therapeutic Potential ◽  
Intravenous Glucose ◽  
Dpp Iv ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Independent Effects ◽  
Insulinotropic Effect ◽  
Insulin Responses

Glucagon-like peptide 1 (GLP-1) is a potent anti-hyperglycemic hormone currently under investigation for its therapeutic potential. However, due to rapid degradation by dipeptidyl peptidase IV (DPP IV), which limits its metabolic stability and eliminates its insulinotropic activity, it has been impossible to assess its true efficacy in vivo. In chloralose-anesthetized pigs given valine-pyrrolidide (to block endogenous DPP IV activity), the independent effects of GLP-1-(7–36) amide on glucose and insulin responses to intravenous glucose were assessed, and the metabolite generated by DPP IV, GLP-1-(9–36) amide, was investigated for any ability to influence these responses. GLP-1-(7–36) amide enhanced insulin secretion ( P < 0.03 vs. vehicle), but GLP-1-(9–36) amide was without effect, either alone or when coinfused with GLP-1-(7–36) amide. In contrast, GLP-1-(9–36) amide did affect glucose responses ( P < 0.03). Glucose excursions were greater after saline (121 ± 17 mmol · l−1 · min) than after GLP-1-(9–36) amide (73 ± 19 mmol · l−1 · min; P < 0.05), GLP-1-(7–36) amide (62 ± 13 mmol · l−1 · min; P < 0.02) or GLP-1-(7–36) amide + GLP-1-(9–36) amide (50 ± 13 mmol · l−1 · min; P < 0.005). Glucose elimination rates were faster after GLP-1-(7–36) amide + (9–36) amide (10.3 ± 1.2%/min) than after GLP-1-(7–36) amide (7.0 ± 0.9%/min; P < 0.04), GLP-1-(9–36) amide (6.8 ± 1.0%/min; P < 0.03), or saline (5.4 ± 1.2%/min; P < 0.005). Glucagon concentrations were unaffected. These results demonstrate that GLP-1-(9–36) amide neither stimulates insulin secretion nor antagonizes the insulinotropic effect of GLP-1-(7–36) amide in vivo. Moreover, the metabolite itself possesses anti-hyperglycemic effects, supporting the hypothesis that selective DPP IV action is important in glucose homeostasis.

Liraglutide for psychiatric disorders: clinical evidence and challenges

2018 ◽  
Vol 36 (2) ◽  
Author(s):  
Mehmet Akif Camkurt ◽  
Luca Lavagnino ◽  
Xiang Y. Zhang ◽  
Antonio L Teixeira
Keyword(s):  
Risk Factors ◽  
Psychiatric Disorders ◽  
Clinical Evidence ◽  
Preclinical Studies ◽  
Potential Candidate ◽  
Obesity And Diabetes ◽  
Treatment Of Diabetes ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Diabetes And Obesity

Abstract Obesity and diabetes are both risk factors and consequences of psychiatric disorders. Glucagon like peptide 1 (GLP-1) receptor agonists such as liraglutide are widely used in the treatment of diabetes and obesity. There are considerable amounts of preclinical studies showing the effects of liraglutide on promotion of neurogenesis, while preventing apoptosis and oxidation. Preliminary clinical evidence has suggested that liraglutide could decrease weight gain, improve cognition and prevent cognitive decline. Accordingly, liraglutide has been regarded as a potential candidate for the management of psychiatric disorders. Herein, we will discuss the association between obesity/diabetes and psychiatric disorders, and the emerging use of liraglutide in psychiatry.

Molecular docking studies and 2D analyses of DPP-4 inhibitors as candidates in the treatment of diabetes

2015 ◽  
Vol 11 (11) ◽  
pp. 3188-3193 ◽  
Author(s):  
Simone Queiroz Pantaleão ◽  
Vinicius Gonçalves Maltarollo ◽  
Sheila Cruz Araujo ◽  
Jadson Castro Gertrudes ◽  
Kathia Maria Honorio
Keyword(s):  
Molecular Docking ◽  
Glycemic Control ◽  
Gastric Inhibitory Polypeptide ◽  
Docking Studies ◽  
Molecular Docking Studies ◽  
Insulin Levels ◽  
Biological Target ◽  
Treatment Of Diabetes ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

DPP-4 is an important biological target related to the treatment of diabetes since some inhibitors can lead to an increase in the insulin levels and the prolonged activity of glucagon-like peptide-1 and gastric inhibitory polypeptide, being effective in glycemic control.

Formation of cyclic structure at amino-terminus of glucagon-like peptide-1 exhibited a prolonged half-life in vivo

2012 ◽  
Vol 96 (3) ◽  
pp. 362-370 ◽  
Author(s):  
Zhenghong Cao ◽  
Ying Li ◽  
Lida Tang ◽  
Weiren Xu ◽  
Changxiao Liu ◽  
...  
Keyword(s):  
Half Life ◽  
Amino Terminus ◽  
Cyclic Structure ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

scholarly journals Differential effects of glucagon-like peptide-1 on microvascular recruitment and glucose metabolism in short- and long-term insulin resistance

2015 ◽  
Vol 593 (9) ◽  
pp. 2185-2198 ◽  
Author(s):  
Kim A. Sjøberg ◽  
Stephen Rattigan ◽  
Jacob F. Jeppesen ◽  
Anne-Marie Lundsgaard ◽  
Jens J. Holst ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Metabolism ◽  
Differential Effects ◽  
Short And Long Term ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Microvascular Recruitment

scholarly journals Long‐term efficacy and safety of combined insulin and glucagon‐like peptide‐1 therapy: Evidence from the LEADER trial

2019 ◽  
Vol 21 (11) ◽  
pp. 2450-2458 ◽  
Author(s):  
Cees J. Tack ◽  
Stephan Jacob ◽  
Cyrus Desouza ◽  
Stephen C. Bain ◽  
John B. Buse ◽  
...  
Keyword(s):  
Efficacy And Safety ◽  
Term Efficacy ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1
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