Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada, The Hebrew University Hadassah Medical School, Jerusalem, Israel.
Department of Surgery, The Hebrew University Hadassah Medical Center, Jerusalem, Israel.
Diabetes. 2018 Jun;67(6):1079-1085. doi: 10.2337/db17-1028. Epub 2018 Feb 23.
Bariatric surgery dramatically improves glycemic control, yet the underlying molecular mechanisms remain controversial because of confounding weight loss. We performed sleeve gastrectomy (SG) on obese and diabetic leptin receptor-deficient mice (/). One week postsurgery, mice weighed 5% less and displayed improved glycemia compared with sham-operated controls, and islets from SG mice displayed reduced expression of diabetes markers. One month postsurgery SG mice weighed more than preoperatively but remained near-euglycemic and displayed reduced hepatic lipid droplets. Pair feeding of SG and sham / mice showed that surgery rather than weight loss was responsible for reduced glycemia after SG. Although insulin secretion profiles from islets of sham and SG mice were indistinguishable, clamp studies revealed that SG causes a dramatic improvement in muscle and hepatic insulin sensitivity accompanied by hepatic regulation of hepatocyte nuclear factor-α and peroxisome proliferator-activated receptor-α targets. We conclude that long-term weight loss after SG requires leptin signaling. Nevertheless, SG elicits a remarkable improvement in glycemia through insulin sensitization independent of reduced feeding and weight loss.
减重手术显著改善了血糖控制，但由于体重减轻的混杂因素，其潜在的分子机制仍存在争议。我们对肥胖和糖尿病瘦素受体缺陷型小鼠（/）进行了袖状胃切除术（SG）。手术后 1 周，与假手术对照组相比，小鼠体重减轻 5%，血糖改善，SG 小鼠的胰岛显示出糖尿病标志物表达减少。手术后 1 个月，SG 小鼠的体重超过术前水平，但仍接近正常血糖水平，肝内脂质滴减少。SG 和假手术/小鼠的配对喂养表明，SG 后血糖降低是手术而不是体重减轻所致。尽管来自 sham 和 SG 小鼠胰岛的胰岛素分泌谱没有区别，但钳夹研究显示，SG 导致肌肉和肝脏胰岛素敏感性显著改善，同时伴有肝细胞核因子-α和过氧化物酶体增殖物激活受体-α靶标的调节。我们得出结论，SG 后长期的体重减轻需要瘦素信号。然而，SG 通过胰岛素增敏作用显著改善血糖，而不依赖于减少进食和体重减轻。
