Effect of endogenous GLP-1 on insulin secretion in type 2 diabetes.

Journal Article (Journal Article)

OBJECTIVE: The incretins glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) account for up to 60% of postprandial insulin release in healthy people. Previous studies showed a reduced incretin effect in patients with type 2 diabetes but a robust response to exogenous GLP-1. The primary goal of this study was to determine whether endogenous GLP-1 regulates insulin secretion in type 2 diabetes. METHODS: Twelve patients with well-controlled type 2 diabetes and eight matched nondiabetic subjects consumed a breakfast meal containing D-xylose during fixed hyperglycemia at 5 mmol/l above fasting levels. Studies were repeated, once with infusion of the GLP-1 receptor antagonist, exendin-(9-39) (Ex-9), and once with saline. RESULTS: The relative increase in insulin secretion after meal ingestion was comparable in diabetic and nondiabetic groups (44 +/- 4% vs. 47 +/- 7%). Blocking the action of GLP-1 suppressed postprandial insulin secretion similarly in the diabetic and nondiabetic subjects (25 +/- 4% vs. 27 +/- 8%). However, Ex-9 also reduced the insulin response to intravenous glucose (25 +/- 5% vs. 26 +/- 7%; diabetic vs. nondiabetic subjects), when plasma GLP-1 levels were undetectable. The appearance of postprandial ingested d-xylose in the blood was not affected by Ex-9. CONCLUSIONS: These findings indicate that in patients with well-controlled diabetes, the relative effects of enteral stimuli and endogenous GLP-1 to enhance insulin release are retained and comparable with those in nondiabetic subjects. Surprisingly, GLP-1 receptor signaling promotes glucose-stimulated insulin secretion independent of the mode of glucose entry. Based on rates of D-xylose absorption, GLP-1 receptor blockade did not affect gastric emptying of a solid meal.

Full Text

Duke Authors

Cited Authors

  • Salehi, M; Aulinger, B; Prigeon, RL; D'Alessio, DA

Published Date

  • June 2010

Published In

Volume / Issue

  • 59 / 6

Start / End Page

  • 1330 - 1337

PubMed ID

  • 20215429

Pubmed Central ID

  • PMC2874693

Electronic International Standard Serial Number (EISSN)

  • 1939-327X

Digital Object Identifier (DOI)

  • 10.2337/db09-1253


  • eng

Conference Location

  • United States