GLP-1 and GLP-2 as yin and yang of intestinal lipoprotein production: evidence for predominance of GLP-2-stimulated postprandial lipemia in normal and insulin-resistant states.
GLP-1 and GLP-2 as yin and yang of intestinal lipoprotein production: evidence for predominance of GLP-2-stimulated postprandial lipemia in normal and insulin-resistant states.
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作者：
Hein GJ;Baker C;Hsieh J;Farr S;Adeli K
胰高血糖素样肽（GLP-1和GLP-2）由胰高血糖素原多肽加工而成，并以等摩尔量分泌，但对乳糜微粒（CM）产生相反的作用，GLP-1显著降低餐后乳糜微粒血症，GLP-2增加餐后乳糜微粒血症。在本研究中，我们评价了GLP-1和GLP-2在生理条件下在叙利亚金仓鼠（一种在脂蛋白代谢方面与人类非常相似的模型）中的明显矛盾作用。短时间（30分钟）静脉输注GLP-2导致餐后载脂蛋白B48（apoB 48）和富含TG的脂蛋白（TRL）组分中的甘油三酯（TG）水平显著增加，而GLP-1输注降低了脂质吸收和TRL-TG和apoB 48水平。GLP-1和GLP-2共输注导致脂质吸收净增加以及TRL-TG和apoB 48增加。然而，GLP-1和GLP-2的长时间（120分钟）共输注降低了餐后脂血。阻断二肽基肽酶-4活性导致餐后脂血减少。有趣的是，果糖喂养的胰岛素抵抗仓鼠表现出更明显的反应，包括可能对GLP-2过敏或对GLP-1敏感性降低。总之，在正常生理条件下，GLP-2的作用占主导地位;然而，当GLP-1活性持续时，GLP-1的降血脂作用占主导地位。GLP-1降解的药理学抑制作用使平衡向对致动脉粥样硬化CM颗粒的肠道产生的抑制作用倾斜。
The glucagon-like peptides (GLP-1 and GLP-2) are processed from the proglucagon polypeptide and secreted in equimolar amounts but have opposite effects on chylomicron (CM) production, with GLP-1 significantly reducing and GLP-2 increasing postprandial chylomicronemia. In the current study, we evaluated the apparent paradoxical roles of GLP-1 and GLP-2 under physiological conditions in the Syrian golden hamster, a model with close similarity to humans in terms of lipoprotein metabolism. A short (30-min) intravenous infusion of GLP-2 resulted in a marked increase in postprandial apolipoprotein B48 (apoB48) and triglyceride (TG) levels in the TG-rich lipoprotein (TRL) fraction, whereas GLP-1 infusion decreased lipid absorption and levels of TRL-TG and apoB48. GLP-1 and GLP-2 coinfusion resulted in net increased lipid absorption and an increase in TRL-TG and apoB48. However, prolonged (120-min) coinfusion of GLP-1 and GLP-2 decreased postprandial lipemia. Blocking dipeptidyl peptidase-4 activity resulted in decreased postprandial lipemia. Interestingly, fructose-fed, insulin-resistant hamsters showed a more pronounced response, including possible hypersensitivity to GLP-2 or reduced sensitivity to GLP-1. In conclusion, under normal physiological conditions, the actions of GLP-2 predominate; however, when GLP-1 activity is sustained, the hypolipidemic action of GLP-1 predominates. Pharmacological inhibition of GLP-1 degradation tips the balance toward an inhibitory effect on intestinal production of atherogenic CM particles.
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影响因子：
4.8
作者：
Hansen, L;Deacon, CF;Holst, JJ
通讯作者：
Holst, JJ
影响因子：
8.2
作者：
Hsieh, J.;Longuet, C.;Adeli, K.
通讯作者：
Adeli, K.
影响因子：
5.8
作者：
Lambeir, AM;Proost, P;De Meester, I
通讯作者：
De Meester, I
DOI：
10.1073/pnas.0706890104
发表时间：
2007-09-18
影响因子：
11.1
作者：
Jang, Hyeung-Jin;Kokrashvili, Zaza;Egan, Josephine M.
通讯作者：
Egan, Josephine M.
影响因子：
4.2
作者：
Meier, Juris J;Nauck, Michael A
通讯作者：
Nauck, Michael A