Sex-different hepaticglycogen content and glucose output in rats.
Sex-different hepaticglycogen content and glucose output in rats.
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DOI：
10.1186/1471-2091-11-38
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发表时间：
2010-09-23
期刊：
影响因子：
--
通讯作者：
Tollet-Egnell P
中科院分区：
文献类型：
--
作者：
Gustavsson C;Yassin K;Wahlström E;Cheung L;Lindberg J;Brismar K;Ostenson CG;Norstedt G;Tollet-Egnell P
啮齿类动物肝脏代谢相关基因的表达存在性别差异。为了测试雄性和雌性大鼠肝脏在脂质和碳水化合物代谢方面是否存在差异，生成了全基因组转录谱，并通过测量肝脏脂质和糖原含量、脂肪酸（FA）氧化速率和肝脏葡萄糖输出（HGO）进行补充。后者是在雄性和雌性大鼠肝脏原位灌注的灌注液中测定的。还使用核磁共振（NMR）光谱分析了这些灌注液，以确定其他肝脏衍生代谢物中的推定性别差异。通过分析皮下注射后Akt磷酸化、基因表达和HGO来监测胰岛素的作用。胰岛素注射在肝脏中检测到的约3500种基因产物中，11%在女性中显著较高，11%在男性中较高。许多转录的甘油三酯（TG），胆固醇和极低密度脂蛋白颗粒的生产是女性占主导地位，而脂肪酸氧化，糖原合成和糖原合成的基因是男性占主导地位。与代谢相关的mRNA水平的性别差异在轻度饥饿（禁食12小时），吸收后状态（禁食4小时）相比，更明显。在肝脏TG含量、FA氧化率或酮体或葡萄糖的血液水平方面没有观察到性别差异。然而，男性有较高的肝糖原含量和较高的HGO，以及较高的胰岛素与胰高血糖素水平的比率。基于NMR光谱，雄性动物的肝源性乳酸也较高。HGO被胰岛素抑制，同时Akt磷酸化水平增加，胰岛素敏感性无性别差异。然而，Thr172磷酸化AMP激酶（AMPK）的程度在女性中较高，表明AMPK依赖性作用的程度较高。总之，雄性具有较高的胰岛素与胰高血糖素水平的比率、较高的糖原水平、较低的AMPK磷酸化程度、较高的促胰岛素基因表达和较高的肝葡萄糖输出。这些性别差异可能反映了健康雄性大鼠肝脏对增加的能量需求做出反应的能力更高。
Genes involved in hepatic metabolism have a sex-different expression in rodents. To test whether male and female rat livers differ regarding lipid and carbohydrate metabolism, whole-genome transcript profiles were generated and these were complemented by measurements of hepatic lipid and glycogen content, fatty acid (FA) oxidation rates and hepatic glucose output (HGO). The latter was determined in perfusates from in situ perfusion of male and female rat livers. These perfusates were also analysed using nuclear magnetic resonance (NMR) spectroscopy to identify putative sex-differences in other liver-derived metabolites. Effects of insulin were monitored by analysis of Akt-phosphorylation, gene expression and HGO after s.c. insulin injections. Out of approximately 3 500 gene products being detected in liver, 11% were significantly higher in females, and 11% were higher in males. Many transcripts for the production of triglycerides (TG), cholesterol and VLDL particles were female-predominant, whereas genes for FA oxidation, gluconeogenesis and glycogen synthesis were male-predominant. Sex-differences in mRNA levels related to metabolism were more pronounced during mild starvation (12 h fasting), as compared to the postabsorptive state (4 h fasting). No sex-differences were observed regarding hepatic TG content, FA oxidation rates or blood levels of ketone bodies or glucose. However, males had higher hepatic glycogen content and higher HGO, as well as higher ratios of insulin to glucagon levels. Based on NMR spectroscopy, liver-derived lactate was also higher in males. HGO was inhibited by insulin in parallel with increased phosphorylation of Akt, without any sex-differences in insulin sensitivity. However, the degree of Thr172-phosphorylated AMP kinase (AMPK) was higher in females, indicating a higher degree of AMPK-dependent actions. Taken together, males had higher ratios of insulin to glucagon levels, higher levels of glycogen, lower degree of AMPK phosphorylation, higher expression of gluconeogenic genes and higher hepatic glucose output. Possibly these sex-differences reflect a higher ability for the healthy male rat liver to respond to increased energy demands.
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影响因子：
4.8
作者：
Flores-Morales, A;Ståhlberg, N;Norstedt, G
通讯作者：
Norstedt, G
影响因子：
15.9
作者：
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3.6
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4
作者：
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ROBINSON I C A F