Collagen peptides alleviate hyperglycemia in mice by modulating insulin resistance, glucose metabolism and gut microbiota

Area of Science:

• Biochemistry
• Metabolic Diseases
• Microbiome Research

Background:

• Dipeptidyl peptidase-IV inhibition by collagen peptides (CP) is known.
• The interplay between AMPK-mediated insulin signaling, gut microbiota, and Type 2 Diabetes Mellitus (T2DM) requires further investigation.
• High-fat diet and streptozotocin (STZ) are common methods for inducing T2DM in animal models.

Purpose of the Study:

• To investigate the hypoglycemic mechanisms of CP intervention in a T2DM mouse model.
• To explore the effects of CP on insulin signaling pathways and gut microbiota composition.
• To determine the potential of CP as a therapeutic agent for T2DM.

Main Methods:

• A T2DM mouse model was established using a high-fat diet and STZ.
• Diabetic mice were treated with CP (400 mg/kg/day) for 4 weeks.
• Blood glucose, lipid levels, gut microbiota composition, short-chain fatty acid (SCFA) concentration, serum GLP-1, insulin resistance index, and hepatic gene/protein expression (IRS1, AMPK, GSK3β, PEPCK, FoxO1) were analyzed.

Main Results:

• CP administration significantly alleviated T2DM symptoms and organ damage.
• CP intervention reduced blood glucose and lipid levels, altered gut microbiota (decreased Firmicutes/Bacteroides ratio), and increased SCFA and GLP-1 levels.
• CP upregulated hepatic IRS1, p-AMPK/AMPK, and p-GSK3β/GSK3β, while downregulating PEPCK and FoxO1, promoting glycogen synthesis and insulin sensitivity.

Conclusions:

• CP intervention demonstrates significant hypoglycemic effects in a T2DM mouse model.
• CP modulates gut microbiota, enhances GLP-1 secretion, and improves insulin signaling pathways.
• CP shows potential as a novel therapeutic strategy for managing and preventing T2DM.