Effect of liver fat on insulin clearance
Effect of liver fat on insulin clearance
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DOI：
10.1152/ajpendo.00444.2007
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发表时间：
2007-12-01
影响因子：
5.1
通讯作者：
Yki-Jarvinen, Hannele
中科院分区：
文献类型：
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作者：
Kotronen, Anna;Vehkavaara, Satu;Yki-Jarvinen, Hannele
脂肪肝与空腹高胰岛素血症相关，这可能反映胰岛素清除或肝脏胰岛素作用受损。我们在80名非糖尿病受试者[年龄43 ± 1岁，体重指数（BMI）26.3 ± 0.5 kg/m2]中测定了肝脏脂肪对胰岛素清除率和肝脏胰岛素敏感性的影响。胰岛素清除率和肝脏胰岛素抵抗通过正常血糖高胰岛素血症（胰岛素输注速率0.3 mU . kg（-1）。min（-1）持续240 min）钳夹技术结合输注[3-H-3]葡萄糖和肝脏脂肪的质子磁共振波谱。在高胰岛素血症期间，高肝脂组（15.0 +/- 1.5%）与低肝脂组（1.8 +/- 0.2%）相比，血清胰岛素浓度和高于基础值的增量均保持相似，高肝脂组（15.0 +/- 1.5%）比低肝脂组（1.8 +/- 0.2%）高40%（P < 0.0001），与年龄、性别和BMI无关。胰岛素清除率（ml . kg去脂质量（-1）。min（-1））与肝脂含量呈负相关（r =-0.52，P < 0.0001），与年龄、性别和BMI无关（r =-0.37，P < 0.001）。肝脏脂肪（范围0-41%）引起的胰岛素清除率变化平均解释了空腹血清（fS）-胰岛素浓度变化的27%。受损的胰岛素清除率对fS-胰岛素浓度的贡献随着肝脏脂肪的增加而增加。这意味着胰岛素敏感性的间接指标，如稳态模型评估，高估了高肝脏脂肪含量受试者的胰岛素抵抗。肝脏脂肪含量与胰岛素清除率校正后的fS-胰岛素浓度（r = 0.43，P < 0.0001）和直接测量的肝脏胰岛素敏感性（r =-0.40，P = 0.0002）显著相关。我们的结论是，增加肝脏脂肪与受损的胰岛素清除和肝脏胰岛素抵抗。肝脏胰岛素敏感性与肝脏脂肪含量相关，独立于胰岛素清除率。
A fatty liver is associated with fasting hyperinsulinemia, which could reflect either impaired insulin clearance or hepatic insulin action. We determined the effect of liver fat on insulin clearance and hepatic insulin sensitivity in 80 nondiabetic subjects [age 43 +/- 1 yr, body mass index (BMI) 26.3 +/- 0.5 kg/m(2)]. Insulin clearance and hepatic insulin resistance were measured by the euglycemic hyperinsulinemic (insulin infusion rate 0.3 mU . kg(-1) . min(-1) for 240 min) clamp technique combined with the infusion of [3-H-3] glucose and liver fat by proton magnetic resonance spectroscopy. During hyperinsulinemia, both serum insulin concentrations and increments above basal remained similar to 40% higher (P < 0.0001) in the high (15.0 +/- 1.5%) compared with the low (1.8 +/- 0.2%) liver fat group, independent of age, sex, and BMI. Insulin clearance (ml . kg fat free mass(-1) . min(-1)) was inversely related to liver fat content (r = -0.52, P < 0.0001), independent of age, sex, and BMI (r = -0.37, P < 0.001). The variation in insulin clearance due to that in liver fat (range 0-41%) explained on the average 27% of the variation in fasting serum (fS)-insulin concentrations. The contribution of impaired insulin clearance to fS-insulin concentrations increased as a function of liver fat. This implies that indirect indexes of insulin sensitivity, such as homeostatic model assessment, overestimate insulin resistance in subjects with high liver fat content. Liver fat content correlated significantly with fS-insulin concentrations adjusted for insulin clearance (r = 0.43, P < 0.0001) and with directly measured hepatic insulin sensitivity (r = -0.40, P = 0.0002). We conclude that increased liver fat is associated with both impaired insulin clearance and hepatic insulin resistance. Hepatic insulin sensitivity associates with liver fat content, independent of insulin clearance.