IGF-I deficiency and enhanced insulin sensitivity due to a mutated growth hormone receptor gene in humans
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 p...
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| Published in: | Molecular and cellular endocrinology Vol. 519; p. 111044 |
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| Format: | Journal Article |
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01-01-2021
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| Abstract | 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. |
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| AbstractList | 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. 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. |
| ArticleNumber | 111044 |
| Author | Peña, Gabriela Palacios, María Torres, Carlos Gavilanes, Antonio WD Guevara, Alexandra Bautista, Camila Guevara-Aguirre, Jaime |
| Author_xml | – sequence: 1 givenname: Jaime surname: Guevara-Aguirre fullname: Guevara-Aguirre, Jaime email: jguevara@usfq.edu.ec, guevaraaguirre@yahoo.com organization: Colegio de Ciencias de La Salud, Universidad San Francisco de Quito, Diego de Robles s/n y Pampite, Cumbayá, Quito, Ecuador – sequence: 2 givenname: Carlos surname: Torres fullname: Torres, Carlos organization: Colegio de Ciencias de La Salud, Universidad San Francisco de Quito, Diego de Robles s/n y Pampite, Cumbayá, Quito, Ecuador – sequence: 3 givenname: Gabriela surname: Peña fullname: Peña, Gabriela organization: Colegio de Ciencias de La Salud, Universidad San Francisco de Quito, Diego de Robles s/n y Pampite, Cumbayá, Quito, Ecuador – sequence: 4 givenname: María surname: Palacios fullname: Palacios, María organization: Colegio de Ciencias de La Salud, Universidad San Francisco de Quito, Diego de Robles s/n y Pampite, Cumbayá, Quito, Ecuador – sequence: 5 givenname: Camila surname: Bautista fullname: Bautista, Camila organization: Colegio de Ciencias de La Salud, Universidad San Francisco de Quito, Diego de Robles s/n y Pampite, Cumbayá, Quito, Ecuador – sequence: 6 givenname: Alexandra surname: Guevara fullname: Guevara, Alexandra organization: Instituto de Endocrinología IEMYR, Quito, Ecuador – sequence: 7 givenname: Antonio WD surname: Gavilanes fullname: Gavilanes, Antonio WD organization: Maastricht University, Maastricht, the Netherlands |
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| CitedBy_id | crossref_primary_10_1159_000516407 crossref_primary_10_1016_j_diabres_2022_110228 crossref_primary_10_1016_j_eclinm_2021_100978 crossref_primary_10_3389_fendo_2022_1072313 crossref_primary_10_1016_j_ghir_2022_101460 crossref_primary_10_1016_j_eclinm_2021_101124 |
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