Effects of free fatty acids on hepatic glycogenolysis and gluconeogenesis in conscious dogs

Effects of free fatty acids on hepatic glycogenolysis and gluconeogenesis in conscious dogs
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DOI:
10.1152/ajpendo.00136.2001
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发表时间:
2002-02-01
影响因子:
5.1
通讯作者:
Cherrington, AD
Cherrington, AD
中科院分区:
医学2区
文献类型:
--
作者:
Chu, CA;Sherck, SM;Cherrington, AD

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本研究的目的是确定高水平的游离脂肪酸(FFA)和/或高血糖对肝糖原分解和糖异生的影响。在存在(FFA + HG)或不存在(FFA + EuG)高血糖的情况下,在胰钳下维持禁食18 h的清醒狗的周围注入脂质。在对照研究中,不输注Intralipid,维持正常血糖(EuG)或高血糖(HG)。在所有四组中,胰岛素和胰高血糖素都保持在基础水平。HG组和FFA + HG组动脉血糖水平升高50%。在EuG组和FFA + EuG组中没有变化。在FFA + EuG和FFA + HG组中,动脉血浆FFA增加了140%,但在EuG和HG组中均无显著变化。两组的动脉甘油水平都增加了150%。EuG组总体(3-h)净肝糖原溶解量为196 +/- 26 mg/kg。HG、FFA + EuG和FFA + HG组分别降低96 +/- 20、82 +/- 16和177 +/- 22 mg/kg。EuG组总体(3-h)肝糖异生通量为128 +/- 22 mg/kg,但在高血糖反应中被30 +/- 9 mg/kg抑制。FFA + EuG组和FFA + HG组分别提高59 +/- 12和56 +/- 10 mg/kg。综上所述,血浆游离脂肪酸和甘油含量的增加可显著抑制肝糖原分解,显著促进肝糖异生。
The aim of this study was to determine the effect of high levels of free fatty acids (FFA) and/or hyperglycemia on hepatic glycogenolysis and gluconeogenesis. Intralipid was infused peripherally in 18-h-fasted conscious dogs maintained on a pancreatic clamp in the presence (FFA + HG) or absence (FFA + EuG) of hyperglycemia. In the control studies, Intralipid was not infused, and euglycemia (EuG) or hyperglycemia (HG) was maintained. Insulin and glucagon were clamped at basal levels in all four groups. The arterial blood glucose level increased by 50% in the HG and FFA + HG groups. It did not change in the EuG and FFA + EuG groups. Arterial plasma FFA increased by similar to140% in the FFA + EuG and FFA + HG groups but did not change significantly either in the EuG or HG groups. Arterial glycerol levels increased by similar to150% in both groups. Overall (3-h) net hepatic glycogenolysis was 196 +/- 26 mg/kg in the EuG group. It decreased by 96 +/- 20, 82 +/- 16, and 177 +/- 22 mg/kg in the HG, FFA + EuG, and FFA + HG groups, respectively. Overall (3-h) hepatic gluconeogenic flux was 128 +/- 22 mg/kg in the EuG group, but it was suppressed by 30 +/- 9 mg/kg in response to hyperglycemia. It was increased by 59 +/- 12 and 56 +/- 10 mg/kg in the FFA + EuG and FFA + HG groups, respectively. In conclusion, an increase in plasma FFA and glycerol significantly inhibited hepatic glycogenolysis and markedly stimulated hepatic gluconeogenesis.