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GLP-1 (9-36) amide, cleavage product of GLP-1 (7-36) amide, is a glucoregulatory peptide.
- Source :
-
Obesity (Silver Spring, Md.) [Obesity (Silver Spring)] 2008 Jul; Vol. 16 (7), pp. 1501-9. Date of Electronic Publication: 2008 Apr 17. - Publication Year :
- 2008
-
Abstract
- Objective: Glucagon-like peptide-1 (GLP-1) (7-36) amide is a glucoregulatory hormone with insulinotropic and insulinomimetic actions. We determined whether the insulinomimetic effects of GLP-1 are mediated through its principal metabolite, GLP-1 (9-36) amide (GLP-1m).<br />Methods and Procedures: Glucose turnover during two, 2-h, euglycemic clamps was measured in 12 lean and 12 obese (BMI <25 or >30 kg/m(2)) male and female subject volunteers with normal oral glucose tolerance test. Saline or GLP-1m were infused from 0 to 60 min in each study. Additionally, seven lean and six obese subjects underwent a third clamp in which the GLP-1 receptor (GLP-1R) antagonist, exendin (9-39) amide was infused from -60 to 60 min with GLP-1m from 0 to 60 min.<br />Results: No glucose infusion was required in lean subjects to sustain euglycemia (glucose clamp) during saline or GLP-1m infusions. However, in obese subjects glucose infusion was necessary during GLP-1m infusion alone in order to compensate for a marked (>50%) inhibition of hepatic glucose production (HGP). Plasma insulin levels remained constant in lean subjects but rose significantly in obese subjects after termination of the peptide infusions. During GLP-1R blockade, infusion of glucose was immediately required upon starting GLP-1m infusions in all subjects due to a more dramatic reduction in HGP, as well as a delayed and modest insulinotropic response.<br />Discussion: We conclude that GLP-1m potently inhibits HGP and is a weak insulinotropic agent. These properties are particularly apparent and pronounced in obese but only become apparent in lean subjects during GLP-1 (7-36) receptor blockade. These previously unrecognized antidiabetogenic actions of GLP-1m may have therapeutic usefulness.
- Subjects :
- Adult
Blood Glucose drug effects
Female
Glucagon-Like Peptide 1 administration & dosage
Glucagon-Like Peptide 1 metabolism
Glucagon-Like Peptide-1 Receptor
Glucose Clamp Technique
Glucose Tolerance Test
Humans
Hypoglycemic Agents administration & dosage
Infusions, Parenteral
Liver drug effects
Male
Middle Aged
Peptide Fragments administration & dosage
Peptide Fragments pharmacology
Peptides administration & dosage
Receptors, Glucagon drug effects
Time Factors
Blood Glucose metabolism
Glucagon-Like Peptide 1 analogs & derivatives
Hypoglycemic Agents metabolism
Insulin blood
Liver metabolism
Obesity metabolism
Peptide Fragments metabolism
Peptides metabolism
Receptors, Glucagon metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1930-7381
- Volume :
- 16
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Obesity (Silver Spring, Md.)
- Publication Type :
- Academic Journal
- Accession number :
- 18421270
- Full Text :
- https://doi.org/10.1038/oby.2008.229