1637-P: Acute Hyperinsulinemia Alters Intramuscular 1,2-DAG Species across Metabolic Phenotypes

Intramuscular lipid levels are linked to obesity and type 2 diabetes (T2D). Annotation of the lipid profile is necessary to elucidate the relevance of this association, as certain lipids are more potent in their pathogenic role in insulin resistance. Despite the relationship between insulin action and intramuscular lipid composition, the effect of acute hyperinsulinemia on the myocellular lipid profile is unknown. Basal and insulin-stimulated vastus lateralis muscle was sampled in sedentary lean adults (n = 12), endurance athletes (n = 12), and individuals with obesity with (n = 7) or without T2D (n = 13). A hyperinsulinemic-euglycemic clamp was performed at 40 mU/m²/min insulin with variable dextrose to maintain 90 mg/dL blood glucose. An insulin-stimulated muscle biopsy was performed 1 h into the insulin clamp. Muscle was dissected of extramuscular adipose tissue and then flash frozen. Whole muscle lipidomics analysis was performed by LC-MS/MS. Hyperinsulinemia decreased whole muscle cell total acylcarnitine (AC) levels (p = 0.001) regardless of group. However, only athletes exhibited a decrease in AC C6:0, C14:0, and C16:1 during the insulin clamp (p < 0.001). Triacylglycerol concentrations also decreased during the clamp regardless of group (p = 0.041). There was no significant effect of the clamp on total 1,2-diacylglycerol (DAG). However, many 1,2-DAG species were elevated with acute hyperinsulinemia, such that the change in various long-chain 1,2-DAGs were inversely related to insulin sensitivity (r = -0.35 - -0.45, p < 0.050). Moreover, di-C18:1 and C16:0/20:0 1,2-DAGs were elevated with acute hyperinsulinemia in T2D alone (p < 0.010). Acute hyperinsulinemia did not affect muscle 1,3-DAG, ceramide, nor sphingomyelin total concentrations. While 1,2-DAGs have been implicated in muscle insulin resistance, our results suggest that differential handling of 1,2-DAGs during acute hyperinsulinemia across metabolic phenotypes may further promote decreased insulin sensitivity.