How the hindgut can cure type 2 diabetes. Ileal transposition improves glucose metabolism and beta-cell function in Goto-kakizaki rats through an enhanced Proglucagon gene expression and L-cell number
How the hindgut can cure type 2 diabetes. Ileal transposition improves glucose metabolism and beta-cell function in Goto-kakizaki rats through an enhanced Proglucagon gene expression and L-cell number
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DOI：
10.1016/j.surg.2007.03.001
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发表时间：
2007-07-01
期刊：
影响因子：
3.8
通讯作者：
Donini, Annibale
中科院分区：
文献类型：
--
作者：
Patriti, Alberto;Aisa, Maria Cristina;Donini, Annibale
背景：据推测，由回肠L细胞分泌的胰高血糖素样肽-1 （GLP-1）在减肥手术后2型糖尿病的缓解中起关键作用，其共同特征是加速营养物质向后肠的输送。真正的转位（IT），一种允许l细胞被未消化的食物刺激的操作，被用来验证这一理论。方法：以2型糖尿病大鼠Goto-Kakizaki （GK）和血糖正常的Sprague-Dawley （SD）大鼠为实验对象。评估葡萄糖耐量、胰岛素抵抗、食物摄入、体重、胰腺形态和功能，以跟踪IT对糖尿病的影响。研究了转位回肠完整的GLP-1分泌和基因表达模式，以验证后肠作用的分子基础。结果：在GK大鼠中，IT显著改善了葡萄糖耐量、胰岛素敏感性和急性胰岛素反应，而不影响体重和食物摄入量。免疫组织化学显示重建的胰岛与正常血糖大鼠的胰岛完全相似，并且有β细胞新生的迹象，从外分泌结构开始。与未处理的大鼠相比，GK转位大鼠的GLP-1分泌的特点是对口服葡萄糖的反应更持久。转位回肠中胰高血糖素原、转化酶原1/3 （PC1/3）和嗜铬粒蛋白A的基因表达显著增强。在血糖正常的大鼠中，由于GLP-1的葡萄糖依赖作用，未观察到对葡萄糖代谢和胰腺形态的影响。结论：本研究有力地证明了后肠在Roux-en-Y胃旁路术（GBP）和胆胰分流术（BPD）后糖尿病的缓解中发挥了重要作用。此外，这些研究结果在临床前水平证实了IT是一种可能与非超重2型糖尿病治疗相关的外科手术。轻度肥胖患者。
Background: It has been hypothesized that glucagon-like peptide-1 (GLP-1), secreted by ileal L cells, plays a key-role in the resolution of type 2 diabetes after bariatric operations whose common feature is an expedite nutrient delivery to the hindgut. Real transposition (IT), an operation that permits L-cell stimulation by undigested food, was employed to verify this theory.Methods: IT was carried out in Goto-Kakizaki (GK) type 2 diabetic rats and in euglycemic Sprague-Dawley (SD) rats. Glucose tolerance, insulin resistance, food-intake, body weight, pancreas morphology, and function were evaluated to track the effects of IT on diabetes. Intact GLP-1 secretion and gene expression Pattern of the transposed ileum were investigated to verify the molecular bases of the hindgut action.Results: In GK rats, IT significantly improved glucose tolerance, insulin sensitivity, and acute insulin response without affecting body weight and food intake. Immunohistochemistry revealed remodeled islets Strictly resembling that of euglycemic rats and signs of beta-cell neogenesis starting with exocrine structures. GLP-1 secretion in GK transposed rats was characterized by a more sustained response to oral glucose compared with nontreated rats. Gene expression of Proglucagon, Proconvertase 1/3 (PC1/3), and Chromogranin A in the transposed ileum significantly enhanced. Effects on glucose metabolism and pancreas morphology were not observed in the euglycemic rats as a consequence of the glucose-dependent action of GLP-1.Conclusions: This study gives strong evidences for the crucial role of the hindgut in the resolution of diabetes after Roux-en-Y gastric bypass (GBP) and biliopancreatic diversion (BPD). Moreover, these findings confirm at the preclinical level that IT is a surgical procedure of possible relevance in the therapy of type 2 diabetes in non-overweight. and mildly obese patients.