Abstract
The insulin/insulin-like growth factor-1 (IGF-1) pathway drives an evolutionarily conserved network that regulates lifespan and longevity. Individuals with Laron syndrome who carry mutations in the growth hormone receptor (GHR) gene that lead to severe congenital IGF-1 deficiency with decreased insulin/IGF-1 signaling (IIS) exhibit reduced prevalence rates of acne, diabetes and cancer. Western diet with high intake of hyperglycemic carbohydrates and insulinotropic dairy over-stimulates IIS. The reduction of IIS in Laron subjects unmasks the potential role of persistent hyperactive IIS mediated by Western diet in the development of diseases of civilization and offers a rational perspective for dietary adjustments with less insulinotropic diets like the Paleolithic diet.
Highlights
Recently, Guevara-Aguirre et al reported on 99 Ecuadorian individuals with Laron syndrome due to growth hormone receptor (GHR) deficiency and congenital insulin-like growth factor-1 (IGF-1) deficiency who did not develop type 2 diabetes (T2D) and were almost free of cancer, in contrast to their healthy relatives with normal insulin/IGF-1 signaling (IIS) [1]
Conclusion and future perspectives Laron syndrome with decreased IIS is associated with a reduced prevalence of acne, T2D and cancer
Up-regulated IIS by Western diet appears to promote the development of chronic diseases of civilization
Summary
Guevara-Aguirre et al reported on 99 Ecuadorian individuals with Laron syndrome due to growth hormone receptor (GHR) deficiency and congenital insulin-like growth factor-1 (IGF-1) deficiency who did not develop type 2 diabetes (T2D) and were almost free of cancer, in contrast to their healthy relatives with normal insulin/IGF-1 signaling (IIS) [1]. Western diet shifts the GH/IGF-1 axis to abnormally high levels, just in the opposite direction of low IIS observed in Laron syndrome [1,2] (Figure 1). Extensive consumption of hyperglycemic food with increased glucosemediated signal transduction to pancreatic b-cells is a major factor of glucose/FoxO1-mediated b-cell proliferation and impaired b-cell oxidative stress responses [8,9,10,11]. Continued over-stimulation of pancreatic b-cells by whey protein-driven IIS after the post-weaning period may continuously diminish nuclear FoxO levels, thereby promoting oxidative stress damage of b-cells resulting in early onset of b-cell cellular senescence and apoptosis [26]. It should be mentioned that Laron subjects are not longer lived than normal subjects eating a Western diet and if not properly treated die of cardiovascular diseases
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