Data from: GLP-1 receptor blockade reduces stimulated insulin secretion in fasted subjects with low circulating GLP-1

• Context: Glucagon-like peptide 1 (GLP-1), an insulinotropic peptide released into the circulation from intestinal enteroendocrine cells, is considered a hormonal mediator of insulin secretion. However, the physiological actions of circulating GLP-1 have long been questioned because of the short half-life of the active peptide. Moreover, there is mounting evidence for localized, intra-islet mediation of GLP-1 receptor (GLP-1r) signaling including a role for islet dipeptidyl-peptidase 4 (DPP4).
  
  Objective: To determine whether GLP-1r signaling contributes to insulin secretion in the absence of enteral stimulation and increased plasma levels, and whether this is affected by DPP4.
  Setting: Single-site study conducted at an academic medical center.
  Participants: 20 nondiabetic subjects and 13 subjects with type 2 diabetes.
  Design & Interventions: Cross-over study in which subjects received either a DPP4 inhibitor (DPP4i; sitagliptin) or placebo on two separate days. On each day they received a bolus of intravenous (IV) arginine during sequential 60 minute infusions of the GLP-1r blocker exendin[9-39] (Ex-9) and saline.
  
  Main Outcome Measures: Arginine-stimulated secretion of C-Peptide (C-PArg) and insulin (InsArg).
  
  Results: Plasma GLP-1 remained at fasting levels throughout the experiments and IV arginine stimulated both - and β-cell secretion in all subjects. Ex-9 infusion reduced C-PArg in both the diabetic and nondiabetic groups by ~14% (p < 0.03 for both groups). Sitagliptin lowered baseline glycemia but did not affect the primary measures of insulin secretion. However, a significant interaction between sitagliptin and Ex-9 suggested a greater effect of GLP-1r activation with DPP4i treatment in diabetic subjects.
  Conclusions: GLP-1r activation contributes to β-cell secretion in diabetic and nondiabetic humans during -cell activation, but in the absence of increased circulating GLP-1. These results are compatible with regulation of β-cells by paracrine signals from -cells. This process may be affected by DPP4 inhibition. ... [Read More]

Total Size

5 files (572 KB)

Data Citation

• D'Alessio, D., Gray, S., Hoselton, A., Krishna, R., Slentz, C. (2022). Data from: GLP-1 receptor blockade reduces stimulated insulin secretion in fasted subjects with low circulating GLP-1. Duke Research Data Repository. V2 https://doi.org/10.7924/r41n87v9d

Creator

• Hoselton, Andrew
• Slentz, Cris
• D'Alessio, David
• Krishna, Radha
• Gray, Sarah

DOI

• 10.7924/r41n87v9d

Subject

• GLP-1 receptor
• GLP-1
• Incretin effect
• Insulin secretion
• Glucagon
• Dipeptidyl peptidase 4

Publication Date

• June 16, 2022

ARK

• ark:/87924/r41n87v9d

Replaces

• 10.7924/r4ks6tf5q

Affiliation

• Medicine
• Medicine, Endocrinology, Metabolism, and Nutrition
• Duke Molecular Physiology Institute

Publisher

• Duke Research Data Repository

Type

• Dataset

Format

• CSV
• PDF
• TXT
• XLSX

Related Materials

• Gray SM, Hoselton AL, Krishna R, Slentz CA, D'Alessio DA. GLP-1 Receptor Blockade Reduces Stimulated Insulin Secretion in Fasted Subjects With Low Circulating GLP-1. J Clin Endocrinol Metab. 2022 Aug 18;107(9):2500-2510. doi: 10.1210/clinem/dgac396. PMID: 35775723; PMCID: PMC9387711.  https://doi.org/10.1210/clinem/dgac396

Provenance

• The supplemental PDF file has been updated with a new table (Table 8) after peer-review.

Contact

• David D'Alessio, https://orcid.org/0000-0003-4155-4870, 919-684-5778

License

• Creative Commons CC0 1.0 Universal

Title

• Data from: GLP-1 receptor blockade reduces stimulated insulin secretion in fasted subjects with low circulating GLP-1

License

• http://creativecommons.org/publicdomain/zero/1.0/

Repository

• Duke Research Data Repository

Versions

Version	DOI	Comment	Publication Date
2	10.7924/r41n87v9d	The supplemental PDF file has been updated with a new table (Table 8) after peer-review.	2022-06-16
1	10.7924/r4ks6tf5q		2022-01-26