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首页> 外文期刊>American Journal of Physiology >Impact of in vivo fatty acid oxidation blockade on glucose turnover and muscle glucose metabolism during low-dose AICAR infusion.
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Impact of in vivo fatty acid oxidation blockade on glucose turnover and muscle glucose metabolism during low-dose AICAR infusion.

机译：小剂量AICAR输注期间体内脂肪酸氧化阻断对葡萄糖更新和肌肉葡萄糖代谢的影响。

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摘要

AMPK plays a central role in influencing fuel usage and selection. The aim of this study was to analyze the impact of low-dose AMP analog 5-aminoimidazole-4-carboxamide-1-beta-d-ribosyl monophosphate (ZMP) on whole body glucose turnover and skeletal muscle (SkM) glucose metabolism. Dogs were restudied after prior 48-h fatty acid oxidation (FA(OX)) blockade by methylpalmoxirate (MP; 5 x 12 hourly 10 mg/kg doses). During the basal equilibrium period (0-150 min), fasting dogs (n = 8) were infused with [3-(3)H]glucose followed by either 2-h saline or AICAR (1.5-2.0 mg x kg(-1) x min(-1)) infusions. SkM was biopsied at completion of each study. On a separate day, the same protocol was undertaken after 48-h in vivo FA(OX) blockade. The AICAR and AICAR + MP studies were repeated in three chronic alloxan-diabetic dogs. AICAR produced a transient fall in plasma glucose and increase in insulin and a small decline in free fatty acid (FFA). Parallel increases in hepatic glucose production (HGP), glucose disappearance (R(d tissue)), and glycolytic flux (GF) occurred, whereas metabolic clearance rate of glucose (MCR(g)) did not change significantly. Intracellular SkM glucose, glucose 6-phosphate, and glycogen were unchanged. Acetyl-CoA carboxylase (ACC approximately pSer(221)) increased by 50%. In the AICAR + MP studies, the metabolic responses were modified: the glucose was lower over 120 min, only minor changes occurred with insulin and FFA, and HGP and R(d tissue) responses were markedly attenuated, but MCR(g) and GF increased significantly. SkM substrates were unchanged, but ACC approximately pSer(221) rose by 80%. Thus low-dose AICAR leads to increases in HGP and SkM glucose uptake, which are modified by prior FA(ox) blockade.
机译：AMPK在影响燃油使用和选择方面起着核心作用。这项研究的目的是分析低剂量AMP类似物5-氨基咪唑-4-羧酰胺-1-β-d-核糖基单磷酸（ZMP）对全身葡萄糖更新和骨骼肌（SkM）葡萄糖代谢的影响。在先前的48h脂肪酸被巴氧肟酸甲酯（MP; 5 x 12小时10 mg / kg剂量）阻断后，对狗进行了再研究。在基础平衡期（0-150分钟）内，向禁食的狗（n = 8）注入[3-（3）H]葡萄糖，然后注入2小时盐水或AICAR（1.5-2.0 mg x kg（-1） ）x min（-1））输液。在每次研究完成后对SkM进行活检。在另一天，体内FA（OX）阻断48小时后进行了相同的操作。在三只慢性四氧嘧啶糖尿病狗中重复了AICAR和AICAR + MP研究。 AICAR使血浆葡萄糖短暂下降，胰岛素增加，游离脂肪酸（FFA）略有下降。肝葡萄糖产量（HGP），葡萄糖消失（R（d组织））和糖酵解通量（GF）平行增加，而葡萄糖的代谢清除率（MCR（g））没有明显变化。细胞内SkM葡萄糖，6-磷酸葡萄糖和糖原未改变。乙酰辅酶A羧化酶（ACC大约为pSer（221））增加了50％。在AICAR + MP研究中，对代谢反应进行了修改：120分钟内血糖降低，胰岛素和FFA仅发生微小变化，HGP和R（d组织）反应明显减弱，而MCR（g）和GF明显增加。 SkM底物没有变化，但ACC大约pSer（221）上升了80％。因此，低剂量的AICAR会导致HGP和SkM葡萄糖摄取增加，这可通过先前的FA（ox）阻断来改善。

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