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Enteroendocrine Connections in Congenital Isolated GH Deficiency Due to a GHRH Receptor Gene Mutation

2019; Oxford University Press; Volume: 104; Issue: 7 Linguagem: Inglês

10.1210/jc.2019-00094

1945-7197

Alécia A. Oliveira‐Santos, Roberto Salvatori, Mônica Cristina Nogueira, Ana Carolina Bueno, Cynthia S. Barros-Oliveira, Ângela Cristina Gomes Borges Leal, Cindi G. Marinho, Nayra P. Damascena, D A S Oliveira, Manuela A. Melo, Carla R. P. Oliveira, Flávia Oliveira da Costa, Jéssica S. S. dos Santos, Paula F. C. Santos, Viviane C. Campos, Elenilde G. Santos, Enaldo Vieira de Melo, Meirielly Lima Almeida Barbosa, Ívina E. S. Rocha, Margaret de Castro, Manuel H. Aguiar‐Oliveira,

Metabolism, Diabetes, and Cancer

GH and IGF-1 are crucial for attainment of normal body size and regulation of food intake, nutrient storage, and insulin sensitivity. Enteroendocrine connections exist between the GH–IGF-1 axis and insulin, ghrelin, and glucagon-like peptide 1 (GLP-1). The status of these connections in GH deficiency (GHD) is unknown. To study the enteroendocrine connections before and after a standard meal test in a homogeneous population of adults with congenital untreated isolated GHD (IGHD) due to a mutation in the GHRH receptor gene. In a cross-sectional study of 20 individuals with IGHD and 20 control subjects, we measured glucose, insulin, ghrelin, and GLP-1 before and 30, 60, 120, and 180 minutes after a standardized test meal. Homeostasis model assessment index of insulin resistance (HOMA-IR) and homeostasis model assessment (HOMA)-β were calculated. Participants scored feelings of hunger, fullness, and prospective food consumption on a visual analog scale. Area under the curve (AUC) values of glucose, insulin, ghrelin, GLP-1, hunger, fullness, and prospective food consumption. Fasting HOMA-IR and HOMA-β were lower in individuals with IGHD than in control subjects (P = 0.002 and P = 0.023, respectively). AUC was higher for hunger (P < 0.0001), glucose (P = 0.0157), ghrelin (P < 0.0001), and GLP-1 (P < 0.0001) and smaller for fullness (P < 0.0001) in individuals with IGHD compared with control subjects. There was no difference in AUC for prospective food consumption or insulin. Untreated IGHD is associated with increased GLP-1 secretion and reduced postprandial ghrelin and hunger attenuation in response to a mixed meal. These enteroendocrine connections can result in a favorable outcome in terms of environmental adaptation and guaranteeing appropriate food intake and can confer metabolic benefits.