IGF-I deficiency and enhanced insulin sensitivity due to a mutated growth hormone receptor gene in humans

• Published in: Molecular and cellular endocrinology Vol. 519; p. 111044
• Main Authors: Guevara-Aguirre, Jaime, Torres, Carlos, Peña, Gabriela, Palacios, María, Bautista, Camila, Guevara, Alexandra, Gavilanes, Antonio WD
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01-01-2021
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/j.mce.2020.111044

Human size is achieved by the coordinated expression of many genes. From conception to adulthood, a given genomic endowment is modified by highly variable environmental circumstances. During each stage of a person's life, distinct nutritional and hormonal influences continuously shape growing physical features until mature characteristics are attained. Underlying processes depend on precise provision of substrates and energy extracted by insulin action from nutrients, which allows cell proliferation, differentiation, and survival, under the concerted actions of growth hormone and insulin-like growth factor-I (IGF-I). It should be noted that growth and metabolic signaling pathways are interdependent and superimposed at multiple levels. Attainment of a fully developed human phenotype should be considered as a harmonious increment in body size rather than a simple increase in height. From this perspective we herein analyze adult features of individuals with an inactive growth hormone receptor, who consequently have severely diminished concentrations of serum insulin and endocrine IGF-I.
•GH Receptor (GHR) gene mutations cause Laron syndrome (LS) and generalized GH insensitivity.•LS phenotype includes severe short stature, various malformations, excess body fat and adult obesity.•LS in Ecuador presents with low IGF-I and insulin concentrations.•Absent GH counter-regulation generates decreased insulin resistance, and enhanced insulin sensitivity.•Ecuadorian LS subjects have diminished incidence of type 2 diabetes mellitus and cancer, and a healthier brain.