GLP-1 (9-36) amide, cleavage product of GLP-1 (7-36) amide, is a glucoregulatory peptide

Dariush Elahi, Josephine M. Egan, Richard P. Shannon, Graydon S. Meneilly, Ashok Khatri, Joel F. Habener, Dana Andersen

Research output: Contribution to journalArticle

70 Citations (Scopus)

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). Methods and Procedures: Glucose turnover during two, 2-h, euglycemic clamps was measured in 12 lean and 12 obese (BMI 30 kg/m2) 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. 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. 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.

Original languageEnglish (US)
Pages (from-to)1501-1509
Number of pages9
JournalObesity
Volume16
Issue number7
DOIs
StatePublished - Jul 2008
Externally publishedYes

Fingerprint

Glucose
Peptides
Glucose Clamp Technique
Liver
Glucagon-Like Peptide 1
Glucose Tolerance Test
glucagon-like peptide-1 (9-36)-amide
glucagon-like peptide 1 (7-36)amide
Healthy Volunteers
Hormones
Insulin
Glucagon-Like Peptide-1 Receptor
Therapeutics

ASJC Scopus subject areas

  • Endocrinology
  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

Cite this

Elahi, D., Egan, J. M., Shannon, R. P., Meneilly, G. S., Khatri, A., Habener, J. F., & Andersen, D. (2008). GLP-1 (9-36) amide, cleavage product of GLP-1 (7-36) amide, is a glucoregulatory peptide. Obesity, 16(7), 1501-1509. https://doi.org/10.1038/oby.2008.229

GLP-1 (9-36) amide, cleavage product of GLP-1 (7-36) amide, is a glucoregulatory peptide. / Elahi, Dariush; Egan, Josephine M.; Shannon, Richard P.; Meneilly, Graydon S.; Khatri, Ashok; Habener, Joel F.; Andersen, Dana.

In: Obesity, Vol. 16, No. 7, 07.2008, p. 1501-1509.

Research output: Contribution to journalArticle

Elahi, D, Egan, JM, Shannon, RP, Meneilly, GS, Khatri, A, Habener, JF & Andersen, D 2008, 'GLP-1 (9-36) amide, cleavage product of GLP-1 (7-36) amide, is a glucoregulatory peptide', Obesity, vol. 16, no. 7, pp. 1501-1509. https://doi.org/10.1038/oby.2008.229
Elahi D, Egan JM, Shannon RP, Meneilly GS, Khatri A, Habener JF et al. GLP-1 (9-36) amide, cleavage product of GLP-1 (7-36) amide, is a glucoregulatory peptide. Obesity. 2008 Jul;16(7):1501-1509. https://doi.org/10.1038/oby.2008.229
Elahi, Dariush ; Egan, Josephine M. ; Shannon, Richard P. ; Meneilly, Graydon S. ; Khatri, Ashok ; Habener, Joel F. ; Andersen, Dana. / GLP-1 (9-36) amide, cleavage product of GLP-1 (7-36) amide, is a glucoregulatory peptide. In: Obesity. 2008 ; Vol. 16, No. 7. pp. 1501-1509.
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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). Methods and Procedures: Glucose turnover during two, 2-h, euglycemic clamps was measured in 12 lean and 12 obese (BMI 30 kg/m2) 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. 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. 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.",
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AU - Egan, Josephine M.

AU - Shannon, Richard P.

AU - Meneilly, Graydon S.

AU - Khatri, Ashok

AU - Habener, Joel F.

AU - Andersen, Dana

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