Division of Diabetes, University of Texas Health at San Antonio, San Antonio, TX 78229, USA.
South Texas Veteran Health Care System, Audie Murphy Hospital, San Antonio, TX 78229, USA.
Int J Mol Sci. 2022 Jul 11;23(14):7667. doi: 10.3390/ijms23147667.
Background: The liver has the capacity to regulate glucose metabolism by altering the insulin clearance rate (ICR). The decreased fasting insulin concentrations and enhanced prandial hyperinsulinemia after Roux-en-Y gastric-bypass (GB) surgery and sleeve gastrectomy (SG) are well documented. Here, we investigated the effect of GB or SG on insulin kinetics in the fasting and fed states. Method: ICR was measured (i) during a mixed-meal test (MMT) in obese non-diabetic GB (n = 9) and SG (n = 7) subjects and (ii) during a MMT combined with a hyperinsulinemic hypoglycemic clamp in the same GB and SG subjects. Five BMI-matched and non-diabetic subjects served as age-matched non-operated controls (CN). Results: The enhanced ICR during the fasting state after GB and SC compared with CN (p < 0.05) was mainly attributed to augmented hepatic insulin clearance rather than non-liver organs. The dose-response slope of the total insulin extraction rate (InsExt) of exogenous insulin per circulatory insulin value was greater in the GB and SG subjects than in the CN subjects, despite the similar peripheral insulin sensitivity among the three groups. Compared to the SG or the CN subjects, the GB subjects had greater prandial insulin secretion (ISR), independent of glycemic levels. The larger post-meal ISR following GB compared with SG was associated with a greater InsExt until it reached a plateau, leading to a similar reduction in meal-induced ICR among the GB and SG subjects. Conclusions: GB and SG alter ICR in the presence or absence of meal stimulus. Further, altered ICR after bariatric surgery results from changes in hepatic insulin clearance and not from a change in peripheral insulin sensitivity.
肝脏通过改变胰岛素清除率（ICR）来调节葡萄糖代谢。文献中已有充分记载，行 Roux-en-Y 胃旁路术（GB）和袖状胃切除术（SG）后空腹胰岛素浓度降低和进餐后高胰岛素血症增强。在此，我们研究了 GB 或 SG 对空腹和进食状态下胰岛素动力学的影响。方法：我们在肥胖非糖尿病 GB（n = 9）和 SG（n = 7）受试者中进行混合餐测试（MMT）时测量了 ICR，以及在同一 GB 和 SG 受试者中进行 MMT 并结合高胰岛素-低血糖钳夹时测量了 ICR。5 名 BMI 匹配且非糖尿病的受试者作为年龄匹配的非手术对照组（CN）。结果：与 CN 相比，GB 和 SC 后空腹状态下增强的 ICR（p < 0.05）主要归因于肝胰岛素清除率增加，而不是非肝脏器官。尽管三组之间的外周胰岛素敏感性相似，但外源性胰岛素每循环胰岛素值的总胰岛素提取率（InsExt）的剂量反应斜率在 GB 和 SG 受试者中大于 CN 受试者。与 SG 或 CN 受试者相比，GB 受试者具有更大的餐后胰岛素分泌（ISR），而与血糖水平无关。GB 引起的餐后 ISR 大于 SG，这与更大的 InsExt 相关，直到达到平台期，导致 GB 和 SG 受试者的餐后 ICR 相似降低。结论：GB 和 SG 在存在或不存在进食刺激的情况下改变 ICR。此外，减肥手术后 ICR 的改变是由于肝胰岛素清除率的变化，而不是外周胰岛素敏感性的变化。
