Abstract：
OBJECTIVE: Sodium glucose co-transporter-2 (SGLT2) inhibition lowers glucose levels independently of insulin, leading to reduced insulin secretion and increased lipolysis, resulting in elevated circulating free fatty acids (FFAs). While SGLT2 inhibition improves tissue insulin sensitivity, the increase in circulating FFAs could reduce insulin sensitivity in skeletal muscle and the liver. We aimed to investigate the effects of SGLT2 inhibition on substrate utilization in skeletal muscle and the liver and to measure beta-cell function and glucose tolerance.
METHODS: Thirteen metformin-treated individuals with type 2 diabetes were randomized to once-daily empagliflozin 25 mg or placebo for 4 weeks in a crossover design. Skeletal muscle glucose and FFA uptake together with hepatic tissue FFA uptake were measured using [18F]FDG positron emission tomography/computed tomography (PET/CT) and [11C]palmitate PET/CT. Insulin secretion and action were estimated using the oral minimal model.
RESULTS: Empagliflozin did not affect glucose (0.73 ± 0.30 vs. 1.16 ± 0.64, μmol/g/min p = 0.11) or FFA (0.60 ± 0.30 vs. 0.56 ± 0.3, μmol/g/min p = 0.54) uptake in skeletal muscle. FFA uptake in the liver (21.2 ± 10.1 vs. 19 ± 8.8, μmol/100 ml/min p = 0.32) was unaffected. Empagliflozin increased total beta-cell responsivity (20 ± 8 vs. 14 ± 9, 10-9 min-1, p < 0.01) and glucose effectiveness (2.6 × 10-2 ± 0.3 × 10-2 vs. 2.4 × 10-2 ± 0.3 × 10-2, dL/kg/min, p = 0.02).
CONCLUSIONS: Despite improved beta-cell function and glucose tolerance, empagliflozin does not appear to affect skeletal muscle FFA or glucose uptake.
METHODS: Thirteen metformin-treated individuals with type 2 diabetes were randomized to once-daily empagliflozin 25 mg or placebo for 4 weeks in a crossover design. Skeletal muscle glucose and FFA uptake together with hepatic tissue FFA uptake were measured using [18F]FDG positron emission tomography/computed tomography (PET/CT) and [11C]palmitate PET/CT. Insulin secretion and action were estimated using the oral minimal model.
RESULTS: Empagliflozin did not affect glucose (0.73 ± 0.30 vs. 1.16 ± 0.64, μmol/g/min p = 0.11) or FFA (0.60 ± 0.30 vs. 0.56 ± 0.3, μmol/g/min p = 0.54) uptake in skeletal muscle. FFA uptake in the liver (21.2 ± 10.1 vs. 19 ± 8.8, μmol/100 ml/min p = 0.32) was unaffected. Empagliflozin increased total beta-cell responsivity (20 ± 8 vs. 14 ± 9, 10-9 min-1, p < 0.01) and glucose effectiveness (2.6 × 10-2 ± 0.3 × 10-2 vs. 2.4 × 10-2 ± 0.3 × 10-2, dL/kg/min, p = 0.02).
CONCLUSIONS: Despite improved beta-cell function and glucose tolerance, empagliflozin does not appear to affect skeletal muscle FFA or glucose uptake.
摘要：
目的：钠葡萄糖共转运蛋白-2（SGLT2）抑制降低血糖水平独立于胰岛素，导致胰岛素分泌减少和脂解增加，导致循环游离脂肪酸（FFA）升高。虽然SGLT2抑制改善了组织胰岛素敏感性,循环FFA的增加可降低骨骼肌和肝脏的胰岛素敏感性。我们旨在研究SGLT2抑制对骨骼肌和肝脏底物利用的影响，并测量β细胞功能和葡萄糖耐量。
方法：在交叉设计中，将13名接受二甲双胍治疗的2型糖尿病患者随机分为每日一次25mg依帕列净或安慰剂，为期4周。使用[18F]FDG正电子发射断层扫描/计算机断层扫描（PET/CT）和[11C]棕榈酸酯PET/CT测量骨骼肌葡萄糖和FFA摄取以及肝组织FFA摄取。使用口服最小模型估计胰岛素分泌和作用。
结果：Empagliflozin不影响血糖（0.73±0.30vs.1.16±0.64，μmol/g/minp=0.11）或FFA（0.60±0.30vs.0.56±0.3，μmol/g/minp=0.54）在骨骼肌中的摄取。肝脏中的FFA摄取（21.2±10.1vs.19±8.8，μmol/100ml/minp=0.32）不受影响。Empagliflozin增加总β细胞反应性（20±8vs.14±9,10-9min-1,p<0.01）和葡萄糖有效性（2.6×10-2±0.3×10-2vs.2.4×10-2±0.3×10-2,dL/kg/min,p=0.02)。
结论：尽管改善了β细胞功能和葡萄糖耐量，依帕列净似乎不影响骨骼肌FFA或葡萄糖摄取。
方法：在交叉设计中，将13名接受二甲双胍治疗的2型糖尿病患者随机分为每日一次25mg依帕列净或安慰剂，为期4周。使用[18F]FDG正电子发射断层扫描/计算机断层扫描（PET/CT）和[11C]棕榈酸酯PET/CT测量骨骼肌葡萄糖和FFA摄取以及肝组织FFA摄取。使用口服最小模型估计胰岛素分泌和作用。
结果：Empagliflozin不影响血糖（0.73±0.30vs.1.16±0.64，μmol/g/minp=0.11）或FFA（0.60±0.30vs.0.56±0.3，μmol/g/minp=0.54）在骨骼肌中的摄取。肝脏中的FFA摄取（21.2±10.1vs.19±8.8，μmol/100ml/minp=0.32）不受影响。Empagliflozin增加总β细胞反应性（20±8vs.14±9,10-9min-1,p<0.01）和葡萄糖有效性（2.6×10-2±0.3×10-2vs.2.4×10-2±0.3×10-2,dL/kg/min,p=0.02)。
结论：尽管改善了β细胞功能和葡萄糖耐量，依帕列净似乎不影响骨骼肌FFA或葡萄糖摄取。
