Abstract
Muscle sn-1,2-diacylglycerol (DAG) and C18:0 ceramide accumulation in sarcolemmal and mitochondrial compart-ments have been proposed to regulate muscle insulin sen-sitivity. Here, we evaluated whether weight loss-induced improvements in insulin sensitivity were associated with changes in muscle sn-1,2-DAG and ceramide content in people with obesity and type 2 diabetes. We measured skeletal muscle insulin sensitivity, assessed by using the hyperinsulinemic-euglycemic clamp procedure in conjunc-tion with stable isotopically labeled glucose tracer infusion, and skeletal muscle sn-1,2-DAG and ceramide contents by using liquid chromatography–tandem mass spectrometry after subcellular fractionation and DAG isomer separation in 14 adults with obesity and type 2 diabetes before and after marked (18.6 ± 2.1%) weight loss. Whole-body insulin sensitivity doubled after weight loss. Sarcolemmal sn-1,2-DAG and C18:0 ceramide contents after weight loss were not different from values before weight loss. In contrast, mitochondrial-endoplasmic reticulum (ER) C18:0 ceramide content decreased by ~20% after weight loss (from 2.16 ± 0.08 to 1.71 ± 0.13 nmol/g, P < 0.005). These results suggest a decrease in muscle mitochondrial-ER C18:0 ceramide content could contribute to the beneficial effect of weight loss on skeletal muscle insulin sensitivity.
Original language | English |
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Pages (from-to) | 2055-2064 |
Number of pages | 10 |
Journal | Diabetes |
Volume | 73 |
Issue number | 12 |
DOIs | |
State | Published - Dec 2024 |