A Dose-response Study Examining the Contribution of GLP-1 Receptor Signaling to Glucagon-stimulated Insulin Secretion

  • End date
    Sep 23, 2022
  • participants needed
  • sponsor
    Adrian Vella
Updated on 23 March 2022
Accepts healthy volunteers


The GLP-1 receptor (GLP1R) gene is found on the beta cells of the pancreas. Its role is in the control of blood sugar level by enhancing insulin secretion from the pancreas after eating a meal. The purpose of this research study is to evaluate the role of GLP1R in the response to elevated glucagon concentrations.


Glucagon within the islet can signal the β-cell through GLP1R, and acts as an insulin secretagogue. This signaling is blocked by exendin-9,39. The relative importance of glucagon signaling through its cognate receptor or through GLP1R is unknown. Despite the lower affinity of GLP1R for glucagon, intra-islet concentrations of glucagon are sufficiently high to stimulate GLP1R. The other situation where this may occur is in response to pharmacologic doses of glucagon as used for β-cell function testing or raising peripheral glucagon concentrations above fasting values. The experiments proposed will characterize the role of GLP1R in glucagon's actions on the β-cell and the potential therapeutic role of dual (GLP-1R and glucagon receptor) agonists for the treatment of T2DM and obesity.

Condition Healthy
Treatment Saline, Exendin-9,39
Clinical Study IdentifierNCT04459338
SponsorAdrian Vella
Last Modified on23 March 2022


Yes No Not Sure

Inclusion Criteria

weight-stable, non-diabetic subjects

Exclusion Criteria

Age < 25 or > 65 years (to avoid studying subjects who could have latent type 1 diabetes, or the effects of age extremes in subjects with normal or impaired fasting glucose)
HbA1c ≥5.9%
Use of glucose-lowering agents
For female subjects: positive pregnancy test at the time of enrollment or study
History of prior upper abdominal surgery such as adjustable gastric banding, pyloroplasty and vagotomy
Active systemic illness or malignancy
Symptomatic macrovascular or microvascular disease
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