Effects of Multi-Electrode Renal Denervation on Insulin Sensitivity and Glucose Metabolism in a Canine Model of Type 2 Diabetes Mellitus
Effects of Multi-Electrode Renal Denervation on Insulin Sensitivity and Glucose Metabolism in a Canine Model of Type 2 Diabetes Mellitus
复制标题
多电极肾去神经术对 2 型糖尿病犬模型胰岛素敏感性和葡萄糖代谢的影响
DOI：
10.1016/j.jvir.2017.12.011
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发表时间：
2018-05-01
影响因子：
2.9
通讯作者：
Teng, Gao-Jun
中科院分区：
文献类型：
--
作者：
Pan, Tao;Guo, Jin-He;Teng, Gao-Jun
目的：探讨多电极插管肾去神经对2型糖尿病(T2 DM)犬胰岛素敏感性和糖代谢的影响。材料与方法：33只犬随机分为3组：双侧肾去神经(BRDN)组、左肾去神经(LRDN)组和假手术(Sham)组。分别于术前、术后1个月、2个月、3个月测定体重和血生化指标，并于术前、术后1个月、2个月、3个月行肾血管造影和CT血管造影检查。结果：空腹血糖(9.64+/-1.57 mmol/L vs5.12+/-1.08 mmol/L；P<；0.0001)，空腹胰岛素(16.19+/-1.43mIU/mLvs5.07+/-1.13mIU/mL；P<；0.0001)，胰岛素抵抗稳态模型评估(HOMA-IR；6.95+/-1.33vs1.15+/-0.33)；在3个月的随访中，BRDN组与假手术组相比显著降低。Western印迹分析表明，RDN抑制了糖异生基因，调节了胰岛素的作用，并激活了肝脏中的胰岛素受体-AKT信号级联。CT血管造影和组织病理学检查均未发现肾动脉夹层、动脉瘤、血栓或破裂。结论：多电极导管RDN能有效地减少糖异生和糖原分解，从而改善T2 DM犬模型的胰岛素敏感性和糖代谢。
Purpose: To evaluate the effects of multi-electrode catheter-based renal denervation (RDN) on insulin sensitivity and glucose metabolism in a type 2 diabetes mellitus (T2DM) canine model.Materials and Methods: Thirty-three dogs were divided equally into 3 groups: bilateral renal denervation (BRDN) group, left renal denervation (LRDN) group, and sham operation (SHAM) group. Body weight and blood biochemistry were measured at baseline, 20 weeks, and 32 weeks, and renal angiography and computerized tomographic (CT) angiography were determined before the procedure and 1 month, 2 months, and 3 months after the procedure. Western blot was used to identify the activities of gluconeogenic enzymes and insulin-signaling proteins.Results: Fasting plasma glucose (9.64 +/- 1.57 mmol/L vs 5.12 +/- 1.08 mmol/L; P < .0001), fasting insulin (16.19 +/- 1.43 mIU/mL vs 5.07 +/- 1.13 mIU/mL; P < .0001), and homeostasis-model assessment of insulin resistance (HOMA-IR; 6.95 +/- 1.33 vs 1.15 +/- 0.33; P < .0001) in the BRDN group had significantly decreased at the 3-month follow-up compared with the SHAM group. Western blot analyses showed that RDN suppressed the gluconeogenetic genes, modulated insulin action, and activated insulin receptors-AKT signaling cascade in the liver. CT angiography and histopathologic analyses did not show any dissection, aneurysm, thrombus, or rupture in any of the renal arteries.Conclusions: These findings identified that multi-electrode catheter-based RDN could effectively decrease gluconeogenesis and glycogenolysis, resulting in improvements in insulin sensitivity and glucose metabolism in a T2DM canine model.