Sources of plasma glucose and liver glycogen in fasted ob/ob mice
Sources of plasma glucose and liver glycogen in fasted ob/ob mice
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DOI：
10.1007/s00592-005-0201-3
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发表时间：
2005-12-01
影响因子：
3.8
通讯作者：
Hellerstein, MK
中科院分区：
文献类型：
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作者：
Turner, SM;Linfoot, PA;Hellerstein, MK
通过使用双同位素示踪剂输注，在体内研究了ob/ob小鼠肝内碳水化合物通量的变化和急性瘦素给药的影响。在禁食20 h的小鼠中测定了血浆葡萄糖（糖原生成（GNG）和糖原分解）和肝糖原（GNG，直接合成和预先存在）的代谢来源，小鼠输注[2- 13 C1]甘油和[U13 C6]葡萄糖3 h。用同位素稀释法测定总葡萄糖排出量（TGO）和血浆甘油出现率（Ra）。用质量同位素分布分析法（MIDA）测定肝糖原合成的直接途径GNG和肝磷酸丙糖通量。同时测定血清葡萄糖、胰岛素、瘦素和肝糖原浓度。禁食24小时后，与对照组相比，ob/ob小鼠的TGO高2倍，肝糖原含量高2.5倍，糖原分解葡萄糖的通量、绝对GNG和直接糖原合成率（增加10倍）明显更高。与对照组相比，Ob/ob小鼠的磷酸丙糖通量也升高（40 vs. 22 mg/kg瘦体重/min）。本文提出了一种控制和ob/ob小鼠肝内流量分布的模型。总之，空腹血糖浓度升高是由于ob/ob小鼠中TGO增加所致，其通过GNG增加和糖原分解增加维持。此外，ob/ob小鼠在空腹肝脏碳水化合物流入磷酸丙糖池和糖原方面有重大改变。我们支持瘦素对肝脏葡萄糖代谢的作用需要胰岛素或其他因素的模型。
Alterations in intrahepatic carbohydrate fluxes in ob/ob mice and the effects of acute leptin administration were studied in vivo by use of a dual-isotope tracer infusion. Metabolic sources of plasma glucose (gluconeogenesis (GNG) and glycogenolysis) and hepatic glycogen (GNG, direct synthesis and pre-existing) were determined in 20-h-fasted mice infused with [2-13C1]glycerol and [U13C6]glucose for 3 h. Total glucose output (TGO) and the rate of appearance (Ra) of plasma glycerol were measured by isotope dilution. GNG, the direct pathway of hepatic glycogen synthesis and hepatic triose-phosphate flux were determined by mass isotopomer distribution analysis (MIDA). Serum glucose, insulin, leptin and liver glycogen concentrations were also measured. After a 24-h fast, ob/ob mice had 2-fold higher TGO, 2.5-fold elevated liver glycogen content and markedly higher glycogenolytic flux to glucose, absolute GNG and direct glycogen synthesis rates (10-fold increased) compared to the control group. Ob/ob mice also had elevated triose-phosphate flux compared to controls (40 vs. 22 mg/kg lean body mass/min). A model of intrahepatic flux distributions in control and ob/ob mice is presented. In summary, elevated fasting plasma glucose concentrations are due to increased TGO in ob/ob mice, which is maintained by both increased GNG and increased glycogenolysis. Furthermore, the ob/ob mice have major alterations in fasting hepatic carbohydrate fluxes into triose-phosphate pools and glycogen. We support the model that actions of leptin on hepatic glucose metabolism require insulin or other factors.