Glucagon-like peptide-1: The missing link in the metabolic clock?

Area of Science:

• Metabolic physiology
• Chronobiology
• Endocrinology

Background:

• Circadian rhythms regulate peripheral tissue functions, including nutrient handling and insulin secretion.
• Glucagon-like peptide-1 (GLP-1) is a key incretin hormone linking nutrient intake to insulin release.
• The role of GLP-1 in the peripheral metabolic clock remains unclear.

Purpose of the Study:

• To investigate if intestinal GLP-1 secretion follows a circadian pattern.
• To determine if circadian disruption affects GLP-1 secretion and glucose metabolism.
• To explore the presence and function of clock genes in intestinal L-cells.

Main Methods:

• Studied GLP-1 secretion patterns in rats and humans in vivo.
• Assessed the impact of circadian disruptors (constant light, Western diet, mistimed feeding) on GLP-1 and insulin rhythms.
• Analyzed glucose tolerance in response to circadian disruption.
• Detected circadian clock gene expression and GLP-1 secretion from murine and human L-cells in vitro.

Main Results:

• Intestinal GLP-1 secretion exhibits a circadian rhythm in rats and humans.
• Circadian disruptors alter GLP-1 secretion rhythms, paralleling impaired insulin responses and glucose tolerance.
• Circadian clock gene expression and rhythmic GLP-1 secretion were confirmed in L-cells in vitro.

Conclusions:

• GLP-1 is a functional component of the peripheral metabolic clock.
• Altered GLP-1 release due to circadian disruption may contribute to metabolic dysregulation.
• These findings highlight the importance of circadian alignment for metabolic health.