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The effects of kisspeptin on ?-cell function, serum metabolites and appetite in humans.

ABSTRACT: 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 ?-cell line (EndoC-?H1 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.

SUBMITTER: Izzi-Engbeaya C

PROVIDER: S-EPMC6282711 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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The effects of kisspeptin on β-cell function, serum metabolites and appetite in humans.

Izzi-Engbeaya Chioma C Comninos Alexander N AN Clarke Sophie A SA Jomard Anne A Yang Lisa L Jones Sophie S Abbara Ali A Narayanaswamy Shakunthala S Eng Pei Chia PC Papadopoulou Deborah D Prague Julia K JK Bech Paul P Godsland Ian F IF Bassett Paul P Sands Caroline C Camuzeaux Stephane S Gomez-Romero Maria M Pearce Jake T M JTM Lewis Matthew R MR Holmes Elaine E Nicholson Jeremy K JK Tan Tricia T Ratnasabapathy Risheka R Hu Ming M Carrat Gaelle G Piemonti Lorenzo L Bugliani Marco M Marchetti Piero P Johnson Paul R PR Hughes Stephen J SJ James Shapiro A M AM Rutter Guy A GA Dhillo Waljit S WS

Diabetes, obesity & metabolism 20180816 12

<h4>Aims</h4>To investigate the effect of kisspeptin on glucose-stimulated insulin secretion and appetite in humans.<h4>Materials and methods</h4>In 15 healthy men (age: 25.2 ± 1.1 years; BMI: 22.3 ± 0.5 kg m<sup>-2</sup> ), we compared the effects of 1 nmol kg<sup>-1</sup> h<sup>-1</sup> 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 ins ...[more]

PMID: 29974637

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Project description:Kisspeptin is a peptide encoded by the Kiss 1 gene and is also called metastin. Previous studies have generally focused on several functions of this peptide, including metastasis, puberty, vasoconstriction and reproduction. However, few studies have focused on the cardiac functions of kisspeptin. In the present study, cardiac histomorphology was observed via TEM (transmission electron microscope) and HE and Masson staining to observe instinctive changes. Serum metabolites levels were also measured and analyzed using GC/TOF-MS after injection with kisspeptin-10. A gene chip was employed to screen the potential genes and pathways in the myocardium at the transcriptional leve, while RT-PCR and Western Blot were conducted to verify the relevant mRNA and protein expression, respectively. Histopathological findings demonstrated that there were many irregular wavy contractions through HE staining and increased fibrosis around the heart cells through Masson staining after treatment with kisspeptin-10. Additionally, the main changes in ultrastructure, including changes in mitochondrial and broken mitochondrial cristae, could be observed with TEM after treatment with kisspeptin-10. The PCA scores plot of the serum metabolites was in the apparent partition after injection of kisspeptin-10. Twenty-six obviously changed metabolites were detected and classified as amino acids, carbohydrate metabolites, organic acids and other metabolites. Furthermore, gene chip analysis showed 1112 differentially expressed genes after treatment with kisspeptin-10, including 330 up-regulated genes and 782 down-regulated genes. These genes were enriched in several signaling pathways related to heart diseases. The RT-PCR result for ITGB8, ITGA4, ITGB7, MYL7, HIF1-α and BNP corresponded with the gene chip assay. Moreover, the upregulated genes ITGB8, ITGA4 and BNP also displayed consistent protein levels in Western Blot results. In summary, these findings suggest that kisspeptin-10 could alter the morphology and structure of myocardial cells, serum metabolite levels, and expression of genes and proteins in heart tissues. Our work determined the profound effects of kisspeptin-10 on the heart, which could further lead to the development of therapeutics related to kisspeptin-10, including antagonists and analogs.

Project description:The hypothalamic peptide oxytocin and its receptor are involved in a range of physiological processes, including parturition, lactation, cell growth, wound healing, and social behavior. More recently, increasing evidence has established the effects of oxytocin on food intake, energy expenditure, and peripheral metabolism. In this review, we provide a comprehensive description of the central oxytocinergic system in which oxytocin acts to shape eating behavior and metabolism. Next, we discuss the peripheral beneficial effects oxytocin exerts on key metabolic organs, including suppression of visceral adipose tissue inflammation, skeletal muscle regeneration, and bone tissue mineralization. A brief summary of oxytocin actions learned from animal models is presented, showing that weight loss induced by chronic oxytocin treatment is related not only to its anorexigenic effects, but also to the resulting increase in energy expenditure and lipolysis. Following an in-depth discussion on the technical challenges related to endogenous oxytocin measurements in humans, we synthesize data related to the association between endogenous oxytocin levels, weight status, metabolic syndrome, and bone health. We then review clinical trials showing that in humans, acute oxytocin administration reduces food intake, attenuates fMRI activation of food motivation brain areas, and increases activation of self-control brain regions. Further strengthening the role of oxytocin in appetite regulation, we review conditions of hypothalamic insult and certain genetic pathologies associated with oxytocin depletion that present with hyperphagia, extreme weight gain, and poor metabolic profile. Intranasal oxytocin is currently being evaluated in human clinical trials to learn whether oxytocin-based therapeutics can be used to treat obesity and its associated sequela. At the end of this review, we address the fundamental challenges that remain in translating this line of research to clinical care.

Dataset Information

The effects of kisspeptin on ?-cell function, serum metabolites and appetite in humans.

Publications

The effects of kisspeptin on β-cell function, serum metabolites and appetite in humans.

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