Oral Cooked Foods AGEs Promote Diabetes
The epidemics of insulin resistance (IR) and type 2 diabetes (T2D) affect the first world as well as less-developed countries, and now affect children as well. Persistently elevated oxidative stress and inflammation (OS/Infl) precede these polygenic conditions.
A hallmark of contemporary lifestyle is a preference for cooked foods, replete with pro-OS/Infl advanced glycation endproducts (AGEs), which enhance appetite and cause over-nutrition. We propose that chronic ingestion of oral AGEs promotes insulin resistance and T2D. The mechanism(s) involved in these findings were assessed in four generations of C57BL6 mice fed isocaloric diets with or without AGEs [synthetic methyl-glyoxal-derivatives (MG+)].
F3/MG+ mice manifested increased adiposity and premature insulin resistance, marked by severe deficiency of anti-AGE advanced glycation receptor 1 (AGER1) and of survival factor sirtuin 1 (SIRT1) in white adipose tissue (WAT), skeletal muscle, and liver. Impaired 2-deoxy-glucose uptake was associated with marked changes in insulin receptor (InsR), IRS-1, IRS-2, Akt activation, and a macrophage and adipocyte shift to a pro-OS/inflammatory (M1) phenotype. These features were absent in F3/MG− mice. MG stimulation of 3T3-L1 adipocytes led to suppressed AGER1 and SIRT1, and altered InsR, IRS-1, IRS-2 phosphorylation, and nuclear factor kappa-light chain enhancer of activated B cells (Nf-κB) p65 acetylation. Gene modulation revealed these effects to be coregulated by AGER1 and SIRT1.
Thus, prolonged oral exposure to MG-AGEs can deplete host-defenses AGER1 and SIRT1, raise basal OS/Infl, and increase susceptibility to dysmetabolic insulin resistance. Because exposure to AGEs can be decreased, these insights provide an important framework for alleviating a major lifestyle-linked disease epidemic.
Understanding that eating cooked foods on a regular basis, particularly grilled, fried, baked and broiled foods, depletes our defenses and increases our susceptibility to insulin resistance and type 2 diabetes suggests that we consider changing our eating habits to include more raw, whole, fresh foods. The Roman Diet emphasizes the same.
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