Document Detail


Incretins and other peptides in the treatment of diabetes.
MedLine Citation:
PMID:  17263764     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Glucagon-like peptide-1 (7-36) amide (GLP-1) is a gut hormone, released postprandially,which stimulates insulin secretion and insulin gene expression as well as pancreatic B-cell growth. Together with glucose-dependent insulinotropic polypeptide (GIP), it is responsible for the incretin effect which is the augmentation of insulin secretion following oral administration of glucose. Patients with Type 2 diabetes have greatly impaired or absent incretin-mediated insulin secretion which is mainly as a result of decreased secretion of GLP-1. However,the insulinotropic action of GLP-1 is preserved in patients with Type 2 diabetes,and this has encouraged attempts to treat Type 2 diabetic patients with GLP-1.GLP-1 also possesses a number of potential advantages over existing agents for the treatment of Type 2 diabetes. In addition to stimulating insulin secretion and promoting pancreatic B-cell mass, GLP-1 suppresses glucagon secretion,delays gastric emptying and inhibits food intake. Continuous intravenous and subcutaneous administration significantly improves glycaemic control and causes reductions in both HbA1c and body weight. However, GLP-1 is metabolized extremely rapidly in the circulation by the enzyme dipeptidyl peptidase IV(DPP-IV). This is the probable explanation for the short-lived effect of single doses of native GLP-1, making it an unlikely glucose-lowering agent. The DPP-IV resistant analogue, exenatide, has Food and Drug Administration (FDA) approval for the treatment of Type 2 diabetes and selective DPP-IV inhibitors are underdevelopment. Both approaches have demonstrated remarkable efficacy in animal models and human clinical studies. Both are well tolerated and appear to have advantages over current therapies for Type 2 diabetes, particularly in terms of the effects on pancreatic B-cell restoration and potential weight loss.
Authors:
J F Todd; S R Bloom
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Diabetic medicine : a journal of the British Diabetic Association     Volume:  24     ISSN:  0742-3071     ISO Abbreviation:  Diabet. Med.     Publication Date:  2007 Mar 
Date Detail:
Created Date:  2007-03-30     Completed Date:  2007-08-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8500858     Medline TA:  Diabet Med     Country:  England    
Other Details:
Languages:  eng     Pagination:  223-32     Citation Subset:  IM    
Affiliation:
Department of Metabolic Medicine, Imperial College London, Hammersmith Hospital, London, UK.
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MeSH Terms
Descriptor/Qualifier:
Antigens, CD26 / metabolism
Diabetes Mellitus, Type 2 / drug therapy*
Glucagon-Like Peptide 1 / metabolism,  therapeutic use*
Humans
Hypoglycemic Agents / therapeutic use*
Insulin-Secreting Cells / metabolism*
Peptides / metabolism,  therapeutic use
Venoms / metabolism,  therapeutic use
Weight Loss / drug effects*
Chemical
Reg. No./Substance:
0/Hypoglycemic Agents; 0/Peptides; 0/Venoms; 141732-76-5/exenatide; 89750-14-1/Glucagon-Like Peptide 1; EC 3.4.14.5/Antigens, CD26

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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