GLP-1R responsiveness predicts individual gastric bypass efficacy on glucose tolerance in rats.
GLP-1R responsiveness predicts individual gastric bypass efficacy on glucose tolerance in rats.
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作者：
Habegger KM;Heppner KM;Amburgy SE;Ottaway N;Holland J;Raver C;Bartley E;Müller TD;Pfluger PT;Berger J;Toure M;Benoit SC;Dimarchi RD;Perez-Tilve D;D'Alessio DA;Seeley RJ;Tschöp MH
目前有几种减肥手术用于治疗肥胖和与肥胖相关的合并症。这些药物的疗效各不相同，但大多数都比目前的药物治疗更有效。Roux-en-Y胃旁路术（RYGB）产生大量体重（BW）减轻和葡萄糖耐量增强，并与肠道激素胰高血糖素样肽1（GLP-1）分泌增加相关。鉴于基于GLP-1的药物在降低血糖水平和BW方面的成功，我们假设对GLP-1受体激动剂的个体敏感性可以预测与GLP-1分泌增加相关的手术的代谢益处。在毒蜥外泌肽-4（Ex 4）给药期间，监测197只高脂饮食诱导的肥胖雄性Long-Evans大鼠的BW损失。基于Ex 4诱导的BW损失和GLP-1诱导的葡萄糖耐量改善，确定了稳定的应答者和非应答者群体。Ex 4极端应答者和无应答者的亚群接受了RYGB手术。在RYGB后，反应者和无反应者显示与假手术相比相似的体重损失，但无反应者保留糖耐量受损。这些数据表明，GLP-1反应测试可以预测RYGB后观察到的一些但不是全部改善。这些发现为基于对GLP-1生物学的更好理解优化减肥手术的使用提供了机会，并为代谢综合征的更个性化治疗方法提供了机会。
Several bariatric operations are currently used to treat obesity and obesity-related comorbidities. These vary in efficacy, but most are more effective than current pharmaceutical treatments. Roux-en-Y gastric bypass (RYGB) produces substantial body weight (BW) loss and enhanced glucose tolerance, and is associated with increased secretion of the gut hormone glucagon-like peptide 1 (GLP-1). Given the success of GLP-1–based agents in lowering blood glucose levels and BW, we hypothesized that an individual sensitivity to GLP-1 receptor agonism could predict metabolic benefits of surgeries associated with increased GLP-1 secretion. One hundred ninety-seven high-fat diet–induced obese male Long-Evans rats were monitored for BW loss during exendin-4 (Ex4) administration. Stable populations of responders and nonresponders were identified based on Ex4-induced BW loss and GLP-1–induced improvements in glucose tolerance. Subpopulations of Ex4 extreme responders and nonresponders underwent RYGB surgery. After RYGB, responders and nonresponders showed similar BW loss compared with sham, but nonresponders retained impaired glucose tolerance. These data indicate that the GLP-1 response tests may predict some but not all of the improvements observed after RYGB. These findings present an opportunity to optimize the use of bariatric surgery based on an improved understanding of GLP-1 biology and suggest an opportunity for a more personalized therapeutic approach to the metabolic syndrome.
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影响因子：
2.9
作者：
Chambers, Adam P.;Stefater, Margaret A.;Wilson-Perez, Hilary E.;Jessen, Lene;Sisley, Stephanie;Ryan, Karen K.;Gaitonde, Shrawan;Sorrell, Joyce E.;Toure, Mouhamadoul;Berger, Jose;D'Alessio, David A.;Sandoval, Darleen A.;Seeley, Randy J.;Woods, Stephen C.
通讯作者：
Woods, Stephen C.
影响因子：
9.5
作者：
Moberly SP;Mather KJ;Berwick ZC;Owen MK;Goodwill AG;Casalini ED;Hutchins GD;Green MA;Ng Y;Considine RV;Perry KM;Chisholm RL;Tune JD
通讯作者：
Tune JD
DOI：
10.1038/ijo.2011.158
发表时间：
2012-06
期刊：
International journal of obesity (2005)
影响因子：
--
作者：
Astrup A;Carraro R;Finer N;Harper A;Kunesova M;Lean ME;Niskanen L;Rasmussen MF;Rissanen A;Rössner S;Savolainen MJ;Van Gaal L;NN8022-1807 Investigators
通讯作者：
NN8022-1807 Investigators
影响因子：
5.8
作者：
Blonde, L.;Klein, E. J.;Kendall, D. M.
通讯作者：
Kendall, D. M.
影响因子：
2.9
作者：
Wickremesekera, K;Miller, G;Stubbs, RS
通讯作者：
Stubbs, RS