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

Author(s):Show less -

Oliveira-Santos, Alecia A. ^[1] ; Salvatori, Roberto ^[2] ; Nogueira, Monica C. ^[3] ; Bueno, Ana C. ^[3] ; Barros-Oliveira, Cynthia S. ^[1] ; Leal, Angela C. G. B. ^[1] ; Marinho, Cindi G. ^[1] ; Damascena, Nayra P. ^[1] ; Oliveira, Djane A. ^[1] ; Melo, Manuela A. ^[1] ; Oliveira, Carla R. P. ^[1] ; da Costa, Flavia O. ^[1] ; dos Santos, Jessica S. S. ^[1] ; Santos, Paula F. C. ^[1] ; Campos, Viviane C. ^[1] ; Santos, Elenilde G. ^[1] ; Melo, Enaldo V. ^[1] ; Barbosa, Meirielly L. A. ^[1] ; Rocha, Ivina E. S. ^[1] ; de Castro, Margaret ^[3] ; Aguiar-Oliveira, Manuel H. ^[1]

Affiliation

^[1] Univ Fed Sergipe, Div Endocrinol, BR-49060100 Aracaju, Sergipe - Brazil

^[2] Johns Hopkins Univ, Sch Med, Div Endocrinol & Metab, Baltimore, MD 21287 - USA

^[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Internal Med, BR-14049900 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM; v. 104, n. 7, p. 2777-2784, JUL 2019.
• Web of Science Citations: 0

Abstract

Context: 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. Objective: 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. Design: 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)-6 were calculated. Participants scored feelings of hunger, fullness, and prospective food consumption on a visual analog scale. Main Outcome Measures: Area under the curve (AUC) values of glucose, insulin, ghrelin, GLP-1, hunger, fullness, and prospective food consumption. Results: Fasting HOMA-IR and HOMA-6 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. Conclusions: 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. (AU)

• FAPESP's process: 14/03989-6 - Uncovering pathophysiological and molecular mechanisms involved in tumorigenesis by platforms for next-generation sequencing (NGS)
• Grantee: Margaret de Castro
• Support Opportunities: Research Projects - Thematic Grants