Obesity, diabetes and cancer: insight into the relationship from a cohort with growth hormone receptor deficiency.
Diabetologia
; 58(1): 37-42, 2015 Jan.
Article
em En
| MEDLINE
| ID: mdl-25316432
ABSTRACT
Obesity with insulin-resistant diabetes and increased cancer risk is a global problem. We consider the alterations of metabolism attendant on the underlying pathogenic overnutrition and the role of the growth hormone (GH)-IGF-1 axis in this interaction. Obesity-induced insulin resistance is a determinant of diabetes. Excess glucose, and an elevated concentration of insulin acting through its own receptors along with complex interactions with the IGF-1 system, will add extra fuel and fuel signalling for malignant growth and induce anti-apoptotic activities, permitting proliferation of forbidden clones. In Ecuador there are ~100 living adults with lifelong IGF-1 deficiency caused by a GH receptor (GHR) mutation who, despite a high percentage of body fat, have markedly increased insulin sensitivity compared with age- and BMI-matched control relatives, and no instances of diabetes, which is present in 6% of unaffected relatives. Only 1 of 20 deceased individuals with GHR deficiency died of cancer vs 20% of ~1,500 relatives. Fewer DNA breaks and increased apoptosis occurred in cell cultures exposed to oxidant agents following addition of serum from GHR-deficient individuals vs serum from control relatives. These changes were reversible by adding IGF-1 to the serum from the GHR-deficient individuals. The reduction in central regulators of pro-ageing signalling thus appears to be the result of an absence of GHR function. The complex inter-relationship of obesity, diabetes and cancer risk is related to excess insulin and fuel supply, in the presence of heightened anti-apoptosis and uninhibited DNA damage when GHR function is normal.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Síndrome de Laron
/
Diabetes Mellitus Tipo 2
/
Neoplasias
/
Obesidade
Tipo de estudo:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Risk_factors_studies
Limite:
Adult
/
Humans
País como assunto:
America do sul
/
Ecuador
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article