Tigerinin

Tigerinin-1R stimulates insulin secretion from pancreatic BRIN-BD11 cells in a glucose-dependent manner at nanomolar concentrations. The mechanism appears to involve G-protein coupled receptor activation leading to cAMP elevation and Ca2+ mobilization, similar to incretin peptides. Notably, tigerinin activity is partially dependent on existing GLP-1 receptor signaling pathways but tigerinins themselves are structurally unrelated to GLP-1.

Unlike GLP-1 and GIP which are rapidly inactivated by dipeptidyl peptidase-4 (DPP-IV), tigerinin-1R has a C-terminal amide and N-terminal structure that confers partial resistance to DPP-IV cleavage. This intrinsic metabolic stability, combined with glucose-dependent insulin secretion (reducing hypoglycemia risk), positions tigerinins as a structurally novel class of anti-diabetic peptide leads distinct from current incretin therapies.

Tigerinin-1 and tigerinin-1R stimulate insulin secretion with EC50 values of 50-300 nM in pancreatic cell lines. In streptozotocin-induced diabetic mouse models, tigerinin peptides improve glucose tolerance and increase insulin levels. The glucose-dependent mechanism reduces hypoglycemia risk relative to sulfonylureas. These findings establish tigerinins as the first frog skin AMP family with direct anti-diabetic potential at physiologically relevant concentrations.

Beyond insulinotropic activity, tigerinins exhibit antimicrobial activity against Gram-positive bacteria, antifungal activity against Candida species, and anti-inflammatory activity through prostaglandin E2 suppression. This multifunctional profile is unusual for such short peptides and suggests multiple simultaneous therapeutic applications for optimized analogs in metabolic and infectious disease contexts.