Regulation of amino acid metabolism and α-cell proliferation by glucagon.
Regulation of amino acid metabolism and α-cell proliferation by glucagon.
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DOI：
10.1111/jdi.12797
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发表时间：
2018-01-03
影响因子：
3.2
通讯作者：
Seino Y
中科院分区：
文献类型：
--
作者：
Hayashi Y;Seino Y
胰高血糖素和胰高血糖素样肽- 1 （GLP - 1）都是由胰高血糖素原通过蛋白水解裂解产生的。阻断胰高血糖素的作用可增加循环中胰高血糖素和GLP‐1的水平，降低血糖水平，并诱导胰岛α‐细胞的增殖。胰高血糖素阻断也抑制肝脏氨基酸分解代谢，提高血清氨基酸水平。在胰高血糖素和GLP‐1均有缺陷的动物模型中，血糖水平没有降低，表明GLP‐1是胰高血糖素阻断术降低血糖水平所必需的。相反，在这种动物模型中观察到α‐细胞增生和高氨基酸酸血症，表明GLP‐1不是调节α‐细胞增殖或氨基酸代谢所必需的。以上结果提示，胰高血糖素对氨基酸代谢的调节比葡萄糖代谢的调节具有更重要的生理功能。虽然胰高血糖素缺乏对葡萄糖代谢的影响可以通过抑制胰岛素分泌来补偿，但对氨基酸代谢的影响却没有。最近，越来越多的数据显示，肝和胰岛α -细胞之间存在一种由胰高血糖素和氨基酸介导的反馈调节机制。然而，关于这一监管机制的一些问题仍有待解决。胰高血糖素作为氨基酸代谢的调节剂，必须仔细考虑胰高血糖素阻滞剂在治疗糖尿病患者中的应用。
Both glucagon and glucagon‐like peptide‐1 (GLP‐1) are produced from proglucagon through proteolytic cleavage. Blocking glucagon action increases the circulating levels of glucagon and GLP‐1, reduces the blood glucose level, and induces the proliferation of islet α‐cells. Glucagon blockade also suppresses hepatic amino acid catabolism and increases the serum amino acid level. In animal models defective in both glucagon and GLP‐1, the blood glucose level is not reduced, indicating that GLP‐1 is required for glucagon blockade to reduce the blood glucose level. In contrast, hyperplasia of α‐cells and hyperaminoacidemia are observed in such animal models, indicating that GLP‐1 is not required for the regulation of α‐cell proliferation or amino acid metabolism. These findings suggest that the regulation of amino acid metabolism is a more important specific physiological role of glucagon than the regulation of glucose metabolism. Although the effects of glucagon deficiency on glucose metabolism are compensated by the suppression of insulin secretion, the effects on amino acid metabolism are not. Recently, data showing a feedback regulatory mechanism between the liver and islet α‐cells, which is mediated by glucagon and amino acids, are accumulating. However, a number of questions on the mechanism of this regulation remain to be addressed. The profile of glucagon as a regulator of amino acid metabolism must be carefully considered for glucagon blockade to be applied therapeutically in the treatment of patients with diabetes.
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影响因子：
82.9
作者：
Hong S;Moreno-Navarrete JM;Wei X;Kikukawa Y;Tzameli I;Prasad D;Lee Y;Asara JM;Fernandez-Real JM;Maratos-Flier E;Pissios P
通讯作者：
Pissios P
影响因子：
29
作者：
Kim J;Okamoto H;Huang Z;Anguiano G;Chen S;Liu Q;Cavino K;Xin Y;Na E;Hamid R;Lee J;Zambrowicz B;Unger R;Murphy AJ;Xu Y;Yancopoulos GD;Li WH;Gromada J
通讯作者：
Gromada J
影响因子：
158.5
作者：
EATON, SB;KONNER, M
通讯作者：
KONNER, M
影响因子：
15.9
作者：
BODEN, G;MASTER, RW;OWEN, OE
通讯作者：
OWEN, OE
DOI：
10.1073/pnas.94.13.6646
发表时间：
1997-06-24
影响因子：
11.1
作者：
Furuta, M;Yano, H;Steiner, DF
通讯作者：
Steiner, DF