The effects of kisspeptin on β-cell function, serum metabolites and appetite in humans.
Izzi-Engbeaya C., Comninos AN., Clarke SA., Jomard A., Yang L., Jones S., Abbara A., Narayanaswamy S., Eng PC., Papadopoulou D., Prague JK., Bech P., Godsland IF., Bassett P., Sands C., Camuzeaux S., Gomez-Romero M., Pearce JTM., Lewis MR., Holmes E., Nicholson JK., Tan T., Ratnasabapathy R., Hu M., Carrat G., Piemonti L., Bugliani M., Marchetti P., Johnson PR., Hughes SJ., James Shapiro AM., Rutter GA., Dhillo WS.
AIMS: To investigate the effect of kisspeptin on glucose-stimulated insulin secretion and appetite in humans. MATERIALS AND METHODS: In 15 healthy men (age: 25.2 ± 1.1 years; BMI: 22.3 ± 0.5 kg m-2 ), we compared the effects of 1 nmol kg-1 h-1 kisspeptin versus vehicle administration on glucose-stimulated insulin secretion, metabolites, gut hormones, appetite and food intake. In addition, we assessed the effect of kisspeptin on glucose-stimulated insulin secretion in vitro in human pancreatic islets and a human β-cell line (EndoC-βH1 cells). RESULTS: Kisspeptin administration to healthy men enhanced insulin secretion following an intravenous glucose load, and modulated serum metabolites. In keeping with this, kisspeptin increased glucose-stimulated insulin secretion from human islets and a human pancreatic cell line in vitro. In addition, kisspeptin administration did not alter gut hormones, appetite or food intake in healthy men. CONCLUSIONS: Collectively, these data demonstrate for the first time a beneficial role for kisspeptin in insulin secretion in humans in vivo. This has important implications for our understanding of the links between reproduction and metabolism in humans, as well as for the ongoing translational development of kisspeptin-based therapies for reproductive and potentially metabolic conditions.