Dual-agonist incretin peptides from fish with potential for obesity-related Type 2 diabetes therapy – A review

The peptides lamprey GLP-1 and paddlefish glucagon significantly lowered blood glucose and elevated plasma insulin in mice.

• Proglucagon-derived peptides from ancient fish function as dual agonists at the GLP1R and glucagon receptor.
• These peptides were the most effective in stimulating insulin release from specific clonal β-cells.
• In a mouse model of obesity and insulin resistance, analogs of these peptides improved glucose tolerance and insulin sensitivity over 21 days.
• Treatment was linked to β-cell proliferation and protection against cell death, along with changes in pancreatic glucagon levels.
• The peptides also altered gene expression related to β-cell function and reduced food intake.
• In insulin-deficient mice, the peptides increased β-cell mass and promoted conversion of glucagon-producing cells to insulin-producing cells.

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