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., Shapiro AMJ., Rutter GA., Dhillo WS.
BACKGROUND: Reproduction and metabolism are inter-dependent, but our understanding of the hormones which regulate both these systems is currently limited. Kisspeptin has well-established crucial roles in mammalian reproduction, and recent reports in animal models suggest kisspeptin may have additional roles in metabolism. However, the effects of kisspeptin on metabolism in humans are as yet unknown. AIMS: To investigate the effect of kisspeptin on glucose-stimulated insulin secretion and appetite in humans. METHODS: In 15 healthy men (age 25.2±1.1years; BMI 22.3±0.5kg.m-2 ), we compared the effects of 1nmol.kg-1 .hr-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 on 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. This article is protected by copyright. All rights reserved.