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Therapeutic Strategies Based on Glucagon-Like Peptide 1
| Content Provider | Paperity |
|---|---|
| Author | Deacon, Carolyn F. |
| Abstract | Glucagon-like peptide (GLP)-1 is an incretin hormone with potent glucose-dependent insulinotropic and glucagonostatic actions, trophic effects on the pancreatic β-cells, and inhibitory effects on gastrointestinal secretion and motility, which combine to lower plasma glucose and reduce glycemic excursions. Furthermore, via its ability to enhance satiety, GLP-1 reduces food intake, thereby limiting weight gain, and may even cause weight loss. Taken together, these actions give GLP-1 a unique profile, considered highly desirable for an antidiabetic agent, particularly since the glucose dependency of its antihyperglycemic effects should minimize any risk of severe hypoglycemia. However, its pharmacokinetic/pharmacodynamic profile is such that native GLP-1 is not therapeutically useful. Thus, while GLP-1 is most effective when administered continuously, single subcutaneous injections have short-lasting effects. GLP-1 is highly susceptible to enzymatic degradation in vivo, and cleavage by dipeptidyl peptidase IV (DPP-IV) is probably the most relevant, since this occurs rapidly and generates a noninsulinotropic metabolite. Strategies for harnessing GLP-1’s therapeutic potential, based on an understanding of factors influencing its metabolic stability and pharmacokinetic/pharmacodynamic profile, have therefore been the focus of intense research in both academia and the pharmaceutical industry. Such strategies include DPP-IV–resistant GLP-1 analogs and selective enzyme inhibitors to prevent in vivo degradation of the peptide. |
| Starting Page | 2181 |
| Ending Page | 2189 |
| File Format | HTM / HTML |
| ISSN | 00121797 |
| DOI | 10.2337/diabetes.53.9.2181 |
| Issue Number | 9 |
| Journal | Diabetes |
| Volume Number | 53 |
| e-ISSN | 1939327X |
| Language | English |
| Publisher | American Diabetes Association |
| Publisher Date | 2004-09-01 |
| Access Restriction | Open |
| Subject Keyword | Dpp-iv, dipeptidyl peptidase iv Glp, glucagon-like peptide Gip, glucose-dependent insulinotropic polypeptide Nep, neutral endopeptidase Oaa, oral antidiabetic agent |
| Content Type | Text |
| Resource Type | Article |
| Subject | Endocrinology, Diabetes and Metabolism Internal Medicine |
