Intestinal CART is a regulator of GIP and GLP-1 secretion and expression.

Area of Science:

• Endocrinology
• Molecular Biology
• Metabolic Diseases

Background:

• The incretin effect is impaired in Type 2 Diabetes (T2D).
• Cocaine- and amphetamine-regulated transcript (CART) peptide regulates pancreatic islet hormone secretion and beta-cell survival.
• The role of CART in incretin regulation is not fully understood.

Purpose of the Study:

• To investigate CART expression in enteroendocrine cells.
• To determine CART's role in regulating incretin secretion and expression.
• To explore CART as a potential therapeutic target for T2D.

Main Methods:

• Immunohistochemical analysis of CART expression in human duodenal and jejunal tissues.
• In vitro studies using GLUTag and STC-1 cell lines to assess CART regulation by nutrients and hormones.
• In vivo studies in mice using oral glucose-tolerance tests to evaluate CART's effect on incretin secretion.

Main Results:

• CART expression was detected in glucose-dependent insulinotropic polypeptide (GIP)-producing K-cells and glucagon-like peptide-1 (GLP-1)-producing L-cells.
• Circulating CART levels increased post-meal in humans.
• Fatty acids and GIP increased CART expression in cell lines, while glucose had no effect.
• CART silencing reduced GLP-1 secretion, and exogenous CART administration enhanced GIP and GLP-1 secretion in vivo.

Conclusions:

• CART is a novel component of human K- and L-cells.
• CART stimulates incretin secretion.
• The CART system represents a potential therapeutic target for managing Type 2 Diabetes.