GLP-1 (7-36) amide restores myocardial insulin sensitivity and prevents the progression of heart failure in senescent beagles.
GLP-1 (7-36) amide restores myocardial insulin sensitivity and prevents the progression of heart failure in senescent beagles.
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DOI：
10.1186/s12933-014-0115-x
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发表时间：
2014-07-31
影响因子：
9.3
通讯作者：
Shannon RP
中科院分区：
文献类型：
--
作者：
Chen M;Angeli FS;Shen YT;Shannon RP
我们之前证明，老年比格犬的全身和心肌胰岛素反应性 (MIR) 受损，而胰高血糖素样肽-1（GLP-1 [7-36] 酰胺）可改善患有扩张型心肌病 (DCM) 的年轻比格犬的 MIR。在这里，我们试图确定衰老是否会导致 DCM 加速，以及 GLP-1 [7-36] 酰胺是否会恢复 MIR 并影响老年比格犬的 DCM 进程。八只年轻的比格犬（Young-Control）和十六只老年比格犬接受了慢性左心室（LV）仪器检查。 7 只老年小猎犬在使用仪器前用 GLP-1 (7–36) 酰胺 (2.5 pmol/kg/min) 治疗 2 周，并在仪器使用后治疗 35 天 (Old + GLP-1)，而其他 9 只作为对照 (Old-Control)。在快速起搏（240 分钟−1）诱发 DCM 之前，所有狗均进行了基线代谢测定和左心室活检以分离线粒体。随着心力衰竭的进展，常规进行血流动力学测量。在基线时，所有老年比格犬的非酯化脂肪酸 (NEFA) 均升高，并且 MIR 受损。 GLP-1降低血浆NEFA（旧对照：853 ± 34；旧 + GLP-1：531 ± 33μmol/L，p < 0.02），改善MIR（旧对照：289 ± 54；旧 + GLP-1： 512 ± 44 mg/min/100 mg，p< 0.05)，并增加分离线粒体中解偶联蛋白 3 (UCP-3) 的表达。与年轻对照相比，老年对照经历了 DCM 病程加速（7 天与 29 天，p< 0.005）和过高的死亡率，而老 + GLP-1 则经历了 DCM 发病潜伏期延长（7 天与 23 天，p< 0.005）并且死亡率降低。衰老与心肌胰岛素抵抗有关，从而导致 DCM 病程加速。 GLP-1 治疗与老年比格犬 MIR 的增加和 DCM 加速进程的保护相关。
We previously demonstrated that older beagles have impaired whole body and myocardial insulin responsiveness (MIR), and that glucagon-like peptide-1 (GLP-1 [7–36] amide) improves MIR in young beagles with dilated cardiomyopathy (DCM). Here, we sought to determine if aging alone predisposes to an accelerated course of DCM, and if GLP-1 [7–36] amide would restore MIR and impact the course of DCM in older beagles. Eight young beagles (Young-Control) and sixteen old beagles underwent chronic left ventricle (LV) instrumentation. Seven old beagles were treated with GLP-1 (7–36) amide (2.5 pmol/kg/min) for 2 weeks prior to instrumentation and for 35 days thereafter (Old + GLP-1), while other 9 served as control (Old-Control). All dogs underwent baseline metabolic determinations and LV biopsy for mitochondria isolation prior to the development of DCM induced by rapid pacing (240 min−1). Hemodynamic measurements were performed routinely as heart failure progressed. At baseline, all old beagles had elevated non-esterifed fatty acids (NEFA), and impaired MIR. GLP-1 reduced plasma NEFA (Old-Control: 853 ± 34; Old + GLP-1: 531 ± 33 μmol/L, p < 0.02), improved MIR (Old-Control: 289 ± 54; Old + GLP-1: 512 ± 44 mg/min/100 mg, p < 0.05), and increased uncoupling protein-3 (UCP-3) expression in isolated mitochondria. Compared to the Young-Control, the Old-Controls experienced an accelerated course of DCM (7 days versus 29 days, p < 0.005) and excess mortality, while the Old + GLP-1 experienced increased latency to the onset of DCM (7 days versus 23 days, p < 0.005) and reduced mortality. Aging is associated with myocardial insulin resistance, which predispose to an accelerated course of DCM. GLP-1 treatment is associated with increased MIR and protection against an accelerated course of DCM in older beagles.
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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：
15.9
作者：
Morino, K;Petersen, KF;Shulman, GI
通讯作者：
Shulman, GI
影响因子：
3.9
作者：
Green, Brian D.;Hand, Katharine V.;Grieve, David J.
通讯作者：
Grieve, David J.
DOI：
10.1016/0735-1097(93)90455-a
发表时间：
1993-10-01
影响因子：
24
作者：
HO, KKL;PINSKY, JL;LEVY, D
通讯作者：
LEVY, D
影响因子：
37.8
作者：
Nikolaidis, LA;Elahi, D;Shannon, RP
通讯作者：
Shannon, RP