INS and metabolic disease: Individuals with IR, T2D, and MASLD have elevated fasting plasma glucose and TG concentrations compared to those without metabolic diseases.27 Findings from rodent models have suggested this may be due to selective resistance to insulin suppressing the GNG pathway but a preservation of insulin sensitivity in stimulating the DNL pathway.3 However, as most studies have focused on either the hepatic GNG or DNL pathway, it remains unclear if both pathways are concurrently upregulated in humans.