Ileal interposition surgery improves glucose and lipid metabolism and delays diabetes onset in the UCD-T2DM rat.
Ileal interposition surgery improves glucose and lipid metabolism and delays diabetes onset in the UCD-T2DM rat.
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DOI：
10.1053/j.gastro.2010.03.005
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发表时间：
2010-06
期刊：
影响因子：
29.4
通讯作者：
Havel PJ
中科院分区：
文献类型：
--
作者：
Cummings BP;Strader AD;Stanhope KL;Graham JL;Lee J;Raybould HE;Baskin DG;Havel PJ
减肥手术已被证明可以逆转2型糖尿病，但其发生的机制仍不明确。回肠间置术（IT）是一种外科手术模型，其隔离了增加未吸收营养物质输送至下胃肠道的影响。在这项研究中，我们研究了IT手术对UCD-T2 DM大鼠（一种2型糖尿病的多基因肥胖动物模型）糖耐量和糖尿病发病的影响。对4月龄雄性UCD-T2 DM大鼠进行IT或假手术。所有动物均接受口服葡萄糖耐量试验（OGTT）。在手术后2个月对一个子集实施安乐死以进行组织分析。其余患者随访至糖尿病发作，并接受口服脂肪耐量试验（OFTT）。与假手术相比，IT手术延迟糖尿病发病120 ± 49天（P< 0.05），但体重无差异。在OGTT期间，与假手术动物相比，IT手术动物表现出较低的血浆葡萄糖波动（P< 0.05），改善的早期胰岛素分泌（P< 0.01）和3倍大的血浆GLP-17-36波动（P< 0.001），并且GIP反应没有差异。在OFTT期间，IT手术动物的总血浆PYY波动大3倍（P< 0.01）。与假手术组相比，IT组动物表现出较低的肥胖（P <0.05），较小的脂肪细胞大小（P< 0.05），异位脂质沉积减少25%，循环脂质降低和胰腺胰岛素含量增加（P< 0.05）。 IT手术延迟了UCD-T2 DM大鼠的糖尿病发作，这可能与营养刺激的GLP-17-36和PYY分泌增加以及胰岛素敏感性、β细胞功能和脂质代谢的改善有关。
Bariatric surgery has been shown to reverse type 2 diabetes, however the mechanisms by which this occurs remain undefined. Ileal interposition (IT) is a surgical model that isolates the effects of increasing the delivery of unabsorbed nutrients to the lower gastrointestinal tract. In this study we investigated the effects of IT surgery on glucose tolerance and diabetes onset in UCD-T2DM rats, a polygenic obese animal model of type 2 diabetes. IT or sham surgery was performed on 4 month old male UCD-T2DM rats. All animals underwent an oral glucose tolerance test (OGTT). A subset was euthanized 2 months after surgery for tissue analyses. The remainder was followed until diabetes onset and underwent an oral fat tolerance test (OFTT). IT surgery delayed diabetes onset by 120 ± 49 days compared with sham surgery (P< 0.05) without a difference in body weight. During OGTT, IT-operated animals exhibited lower plasma glucose excursions (P< 0.05), improved early insulin secretion (P< 0.01) and 3-fold larger plasma GLP-17–36 excursions (P< 0.001) and no difference in GIP responses compared with sham-operated animals. Total plasma PYY excursions during the OFTT were 3-fold larger in IT-operated animals (P< 0.01). IT-operated animals exhibited lower adiposity (P< 0.05), smaller adipocyte size (P< 0.05), 25% less ectopic lipid deposition, lower circulating lipids and greater pancreatic insulin content compared with sham-operated animals (P< 0.05). IT surgery delays the onset of diabetes in UCD-T2DM rats which may be related to increased nutrient-stimulated secretion of GLP-17–36 and PYY and improvements of insulin sensitivity, β-cell function and lipid metabolism.
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DOI：
10.1038/oby.2009.102
发表时间：
2009-09
期刊：
Obesity (Silver Spring, Md.)
影响因子：
--
作者：
Patti ME;Houten SM;Bianco AC;Bernier R;Larsen PR;Holst JJ;Badman MK;Maratos-Flier E;Mun EC;Pihlajamaki J;Auwerx J;Goldfine AB
通讯作者：
Goldfine AB
影响因子：
2.9
作者：
Corradini, SG;Eramo, A;Badiali, M
通讯作者：
Badiali, M
影响因子：
7.7
作者：
Morino, Katsutaro;Petersen, Kitt Falk;Shulman, Gerald I.
通讯作者：
Shulman, Gerald I.
影响因子：
3.8
作者：
Patriti, Alberto;Aisa, Maria Cristina;Donini, Annibale
通讯作者：
Donini, Annibale
影响因子：
5.8
作者：
Boschmann, Michael;Engeli, Stefan;Jordan, Jens
通讯作者：
Jordan, Jens