Is GLP-1 a hormone: Whether and When?

Area of Science:

• Endocrinology
• Metabolism
• Gastroenterology

Background:

• Glucagon-like peptide-1 (GLP-1) is synthesized in the intestine and pancreas and is crucial for glucose tolerance.
• GLP-1 acts via the GLP-1 receptor (GLP-1r), found on pancreatic beta-cells and other tissues.
• The prevailing view is that GLP-1 functions as an endocrine hormone released after meals.

Purpose of the Study:

• To re-evaluate the mechanism of GLP-1 action in physiological conditions versus post-bariatric surgery.
• To investigate whether GLP-1 acts primarily through hormonal, neural, or paracrine pathways.

Main Methods:

• Analysis of GLP-1 concentrations in plasma after meal ingestion.
• Assessment of insulin secretion following systemic GLP-1 receptor antagonism.
• Evaluation of glucose tolerance in mice lacking the GLP-1 receptor in beta-cells.
• Examination of GLP-1 release and its impact on glucose regulation after bariatric surgery.

Main Results:

• Low circulating GLP-1 levels and rapid metabolism challenge the hormonal model.
• Systemic GLP-1 receptor antagonism impairs fasting insulin secretion.
• GLP-1 receptor deletion in beta-cells causes glucose intolerance independent of GLP-1 secretion.
• Bariatric surgery significantly increases postprandial GLP-1, where it mediates insulin secretion.

Conclusions:

• Physiological GLP-1 action is likely mediated by neural or paracrine mechanisms, not endocrine.
• The endocrine action of GLP-1 can be therapeutically exploited, particularly after bariatric surgery.
• GLP-1 receptor signaling is critical for glucose homeostasis, with distinct roles in basal and postprandial states.