| Abstract | Glucagon-like peptide-1 (GLP-1) is a peptide hormone from the gut that stimulates insulin secretion and protects beta-cells, inhibits glucagon secretion and gastric emptying, and reduces appetite and food intake. In agreement with these actions, it has been shown to be highly effective in the treatment of Type 2 diabetes, causing marked improvements in glycaemic profile, insulin sensitivity and beta-cell performance, as well as weight reduction. The hormone is metabolised rapidly by the enzyme dipeptidyl peptidase IV (DPP-IV) and, therefore, cannot be easily used clinically. Instead, resistant analogues of the hormone (or agonists of the GLP-1 receptor) are in development, along with DPP-IV inhibitors, which have been demonstrated to protect the endogenous hormone and enhance its activity. Agonists include both albumin-bound analogues of GLP-1 and exendin-4, a lizard peptide. Clinical studies with exendin have been carried out for > 6 months and have indicated efficacy in patients inadequately treated with oral antidiabetic agents. Orally active DPP-IV inhibitors, suitable for once-daily administration, have demonstrated similar efficacy. Diabetes therapy, based on GLP-1 receptor activation, therefore, appears very promising. |
| Authors | Jens Juul Holst
(Affiliation: The Panum Institute, University of Copenhagen, Denmark. holst at mfi.ku.dk)
|
| Journal | Expert opinion on emerging drugs
(Expert Opin Emerg Drugs)
Vol. 9
Issue 1
Pg. 155-66
(May 2004)
ISSN: 1744-7623 England |
| PMID | 15155141
(Publication Type: Journal Article, Review)
|
| Chemical References |
- CJC 1131
- Glycoproteins
- Hypoglycemic Agents
- Maleimides
- Peptide Fragments
- Peptides
- Protein Precursors
- Receptors, Glucagon
- Venoms
- glucagon-like peptide receptor
- liraglutide
- Insulin
- exenatide
- Proglucagon
- Glucagon-Like Peptide 1
- Glucagon
- Antigens, CD26
- DPP4 protein, human
- Adenosine Deaminase
|
| Topics |
- Adenosine Deaminase
(antagonists & inhibitors, physiology)
- Afferent Pathways
(physiology)
- Animals
- Antigens, CD26
(physiology)
- Appetite
(drug effects)
- Diabetes Mellitus, Experimental
(drug therapy)
- Diabetes Mellitus, Type 2
(drug therapy, physiopathology)
- Drug Therapy, Combination
- Glucagon
(agonists, analogs & derivatives, metabolism, pharmacology, physiology, secretion, therapeutic use)
- Glucagon-Like Peptide 1
- Glycoproteins
(antagonists & inhibitors, physiology)
- Humans
- Hypoglycemic Agents
(administration & dosage, pharmacology, therapeutic use)
- Hypothalamus
(drug effects, physiopathology)
- Insulin
(biosynthesis, genetics, secretion)
- Intestinal Mucosa
(innervation, metabolism)
- Islets of Langerhans
(drug effects, secretion)
- Lizards
- Maleimides
(therapeutic use)
- Mice
- Mice, Knockout
- Mice, Obese
- Peptide Fragments
(agonists, metabolism, pharmacology, physiology)
- Peptides
(pharmacology, therapeutic use)
- Proglucagon
- Protein Precursors
(agonists, metabolism, pharmacology, physiology)
- Rats
- Rats, Zucker
- Receptors, Glucagon
(agonists, deficiency, physiology)
- Venoms
(pharmacology, therapeutic use)
|
