GLP-1 responds to postprandial hyperglycemia by reducing transcription level in grass carp (Ctenopharyngodon idella)

Abstract

Glucagon-like peptide-1 (GLP-1), a member of the proglucagon derived peptide family, is a highly effective incretin to reduce plasma glucose and inhibit food intake in mammals. The physiological function of GLP-1 has been elucidated in some ‘glucose intolerant’ carnivorous fishes. To lay a better understanding in fish glucose intolerance, we synthesized homologous GLP-1 peptide and explored its roles in appetite and glucose regulation under intraperitoneal (IP) injection in herbivorous grass carp which has higher glucose intolerance. The results showed that GLP-1 increased plasma glucose in grass carp. The hyperglycemic effect of the fish GLP-1 was mainly through promoting gluconeogenesis, accompanied by inhibition of glycogen synthesis and stimulation of glycogenolysis pathway. In addition, GLP-1 upregulated the expression of anorexigenic gene (cart) and decreased the orexigenic genes (npy and agrp) expression in grass carp hypothalamus as a conservative way to inhibit the appetite under GLP-1 injection after 2 h. Taken together, the hyperglycemic effect and anorectic role of GLP-1 were performed in a basically consistent manner across fishes with different food habits. What’s more, the gene expressions of proglucagon yielded GLP-1 in foregut and hindgut of grass carp were significantly decreased after a meal within 24 h, indicating that fish might suppress the accumulation of plasma glucose by decreasing GLP-1 expression in a unique way to herbivorous fish. Therefore, this study provided a new perspective for illustrating the difference in glucose utilization among fishes with different food habits based on GLP-1.