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In mouse models of insulin resistance, it significantly inhibits NNMT activity in liver and muscle, reduces NAM methylation, increases intracellular NAD+, activates the SIRT1 pathway, promotes phosphorylation of insulin receptor substrate 1 (IRS1), enhances insulin signaling, improves insulin sensitivity, and increases glucose uptake and utilization
NNMT is an enzyme that methylates nicotinamide (vitamin B3) using S-adenosylmethionine (SAM) as a methyl donor
Because their mechanisms do not overlap, stacking them creates a two-pronged approach: Retatrutide reduces caloric intake and boosts metabolic rate from the top down, while AOD-9604 attacks stored fat at the cellular level from the bottom up
These are often combined with vitamin B12, a nutrient essential for many bodily functions, including energy production and red blood cell formation
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