Glucose-dependent insulinotropic polypeptide (GIP) acts as an appetite regulator rather than as a hypoglycemic incretin in grass carp.

In mammals, glucose-dependent insulinotropic polypeptide (GIP) exerts a potent hypoglycemic effect, whereas its role in fish remains controversial. In this study, synthetic grass carp GIP was administered via intraperitoneal injection, and its effects were evaluated over 24 h. GIP significantly elevated blood glucose levels at 0.5 h post-injection compared to the saline control. This hyperglycemia was accompanied by increased hepatic expression of the gluconeogenic genes glucose-6-phosphatase (g6pc) and phosphoenolpyruvate carboxykinase 1 (pck1) and decreased expression of the glycolytic gene pyruvate kinase (pk). Postprandial expression of the gip gene was also significantly upregulated in the foregut at 6 h. Furthermore, GIP administration modulated central appetite regulators within 1 h, increasing expression of the anorexigenic cocaine- and amphetamine-regulated transcript (cart) and decreasing expression of the orexigenic neuropeptide Y (npy) and agouti related neuropeptide (agrp). Collectively, these results indicate that in grass carp, GIP functions primarily as an appetite regulator rather than as a hypoglycemic incretin, highlighting its potential as a target for studies on appetite control in fish.