Remodeling of hepatic metabolism and hyperaminoacidemia in mice deficient in proglucagon-derived peptides.
Remodeling of hepatic metabolism and hyperaminoacidemia in mice deficient in proglucagon-derived peptides.
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作者：
Watanabe C;Seino Y;Miyahira H;Yamamoto M;Fukami A;Ozaki N;Takagishi Y;Sato J;Fukuwatari T;Shibata K;Oiso Y;Murata Y;Hayashi Y
胰高血糖素被认为是上调血糖水平最重要的肽之一。然而，纯合子胰高血糖素-绿色荧光蛋白（gfp）敲入小鼠（Gcggfp/gfp: GCGKO）尽管缺乏胰高血糖素原衍生肽，包括胰高血糖素，但血糖正常。为了表征GCGKO小鼠的代谢，我们分析了肝脏中的基因表达和代谢组。编码糖异生限速酶的基因表达仅轻微改变。另一方面，编码氨基酸转化为三羧酸循环和/或糖异生代谢产物的酶的基因在GCGKO肝脏中表达较低。参与脂肪酸和烟酰胺代谢的基因表达也发生了改变。GCGKO小鼠肝脏中代谢物浓度的改变与基因表达模式的改变一致，GCGKO小鼠血浆氨基酸浓度升高。GCGKO小鼠血清胰岛素浓度和肝脏Akt蛋白激酶磷酸化水平均降低。这些结果表明胰高血糖素原衍生肽可能在调节多种代谢途径，特别是氨基酸的代谢途径中发挥重要作用。血清胰岛素浓度降低以补偿胰高血糖素原衍生肽缺失对葡萄糖代谢的影响。另一方面，对其他代谢途径的影响只能通过降低胰岛素作用来部分补偿。
Glucagon is believed to be one of the most important peptides for upregulating blood glucose levels. However, homozygous glucagon–green fluorescent protein (gfp) knock-in mice (Gcggfp/gfp: GCGKO) are normoglycemic despite the absence of proglucagon-derived peptides, including glucagon. To characterize metabolism in the GCGKO mice, we analyzed gene expression and metabolome in the liver. The expression of genes encoding rate-limiting enzymes for gluconeogenesis was only marginally altered. On the other hand, genes encoding enzymes involved in conversion of amino acids to metabolites available for the tricarboxylic acid cycle and/or gluconeogenesis showed lower expression in the GCGKO liver. The expression of genes involved in the metabolism of fatty acids and nicotinamide was also altered. Concentrations of the metabolites in the GCGKO liver were altered in manners concordant with alteration in the gene expression patterns, and the plasma concentrations of amino acids were elevated in the GCGKO mice. The insulin concentration in serum and phosphorylation of Akt protein kinase in liver were reduced in GCGKO mice. These results indicated that proglucagon-derived peptides should play important roles in regulating various metabolic pathways, especially that of amino acids. Serum insulin concentration is lowered to compensate the impacts of absent proglucagon-derived peptide on glucose metabolism. On the other hand, impacts on other metabolic pathways are only partially compensated by reduced insulin action.
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影响因子：
4.8
作者：
Furuta, M;Zhou, A;Steiner, DF
通讯作者：
Steiner, DF
影响因子：
64.8
作者：
Alenghat, Theresa;Meyers, Katherine;Mullican, Shannon E.;Leitner, Kirstin;Adeniji-Adele, Adetoun;Avila, Jacqueline;Bucan, Maja;Ahima, Rexford S.;Kaestner, Klaus H.;Lazar, Mitchell A.
通讯作者：
Lazar, Mitchell A.
DOI：
10.1016/j.bbagen.2004.02.009
发表时间：
2004-05-03
影响因子：
3
作者：
Fukuwatari, T;Ohta, M;Shibata, K
通讯作者：
Shibata, K
DOI：
10.1038/nrm3072
发表时间：
2011-03
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.9
作者：
Hagopian, K;Ramsey, JJ;Weindruch, R
通讯作者：
Weindruch, R