Impaired cardiometabolic responses to glucagon-like peptide 1 in obesity and type 2 diabetes mellitus.
Impaired cardiometabolic responses to glucagon-like peptide 1 in obesity and type 2 diabetes mellitus.
复制标题
DOI：
10.1007/s00395-013-0365-x
复制
发表时间：
2013-07
影响因子：
9.5
通讯作者：
Tune JD
中科院分区：
文献类型：
--
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
胰高血糖素样肽 1 (GLP-1) 对心肌葡萄糖摄取具有类似胰岛素的作用，这可能有助于其在心肌缺血的情况下发挥有益作用。这些影响在肥胖或 2 型糖尿病 (T2DM) 的情况下是否有所不同需要调查。我们研究了 GLP-1 (7-36) 在瘦和肥胖/T2DM 人类以及瘦和肥胖 Ossabaw 猪中的心脏代谢作用。 GLP-1 显着增加瘦人静息条件下心肌葡萄糖的摄取，但这种作用在 T2DM 中受到损害。这一观察结果在猪身上得到了证实和扩展，运动期间 GLP-1 增加心肌葡萄糖摄取的作用在瘦猪中可见，但在肥胖猪中却没有。 GLP-1 不会增加人类或猪的心肌耗氧量或血流量。肥胖者心肌对 GLP-1 反应性受损与心肌或冠状动脉 GLP1-R 表达的任何明显改变无关。没有观察到 GLP-1 介导的瘦或肥胖心脏中 cAMP/PKA 或 AMPK 信号传导激活的证据。 GLP-1 治疗可增强瘦心脏组织中的 p38-MAPK 活性，但不会增强肥胖心脏组织中的 p38-MAPK 活性。总而言之，这些数据提供了新的证据，表明 GLP-1 的心脏代谢作用在肥胖和 T2DM 中减弱，其机制可能涉及 p38-MAPK 信号传导受损。
Glucagon-Like Peptide 1 (GLP-1) has insulin-like effects on myocardial glucose uptake which may contribute to its beneficial effects in the setting of myocardial ischemia. Whether these effects are different in the setting of obesity or type 2 diabetes (T2DM) requires investigation. We examined the cardiometabolic actions of GLP-1 (7–36) in lean and obese/T2DM humans, and in lean and obese Ossabaw swine. GLP-1 significantly augmented myocardial glucose uptake under resting conditions in lean humans, but this effect was impaired in T2DM. This observation was confirmed and extended in swine, where GLP-1 effects to augment myocardial glucose uptake during exercise were seen in lean but not in obese swine. GLP-1 did not increase myocardial oxygen consumption or blood flow in humans or in swine. Impaired myocardial responsiveness to GLP-1 in obesity was not associated with any apparent alterations in myocardial or coronary GLP1-R expression. No evidence for GLP-1 mediated activation of cAMP/PKA or AMPK signaling in lean or obese hearts was observed. GLP-1 treatment augmented p38-MAPK activity in lean, but not obese cardiac tissue. Taken together, these data provide novel evidence indicating that the cardiometabolic effects of GLP-1 are attenuated in obesity and T2DM, via mechanisms that may involve impaired p38-MAPK signaling.
登录
查看更多内容
影响因子：
5
作者：
Berwick ZC;Dick GM;Tune JD
通讯作者：
Tune JD
DOI：
10.1161/circheartfailure.109.900282
发表时间：
2010-07
期刊：
Circulation. Heart failure
影响因子：
--
作者：
Bhashyam S;Fields AV;Patterson B;Testani JM;Chen L;Shen YT;Shannon RP
通讯作者：
Shannon RP
影响因子：
8.2
作者：
Hattori, Y.;Jojima, T.;Hayashi, T.
通讯作者：
Hayashi, T.
DOI：
10.1016/j.jss.2009.03.016
发表时间：
2011-01
期刊：
The Journal of surgical research
影响因子：
--
作者：
Matsubara M;Kanemoto S;Leshnower BG;Albone EF;Hinmon R;Plappert T;Gorman JH 3rd;Gorman RC
通讯作者：
Gorman RC
影响因子：
37.8
作者：
Nikolaidis, LA;Elahi, D;Shannon, RP
通讯作者：
Shannon, RP