Deoxycalyxin A lowers blood sugar by activating TGR5 to increase GLP-1 through a specific signaling pathway

Deoxycalyxin A (DCA) significantly reduced fasting blood glucose in db/db mice at doses of 40 and 80 mg/kg.

• DCA is identified as a novel stimulator of GLP-1 secretion in specific cell lines.
• The compound enhances endogenous GLP-1 secretion, which is associated with improved glucose intolerance and insulin resistance.
• Oral administration of DCA also lowered total serum cholesterol levels in db/db mice.
• DCA activates the TGR5 receptor, leading to increased levels of cyclic AMP (cAMP) in cells.
• The activation of cAMP triggers a cascade that includes PKA activation and subsequent phosphorylation of MEK1/2 and ERK.

Simplified