Effects of pioglitazone and metformin on NEFA-induced insulin resistance in type 2 diabetes
Effects of pioglitazone and metformin on NEFA-induced insulin resistance in type 2 diabetes
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DOI：
10.1007/s00125-008-1138-1
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发表时间：
2008-11-01
期刊：
影响因子：
8.2
通讯作者：
Rizza, R. A.
中科院分区：
文献类型：
--
作者：
Basu, R.;Basu, A.;Rizza, R. A.
目的/假设我们试图确定吡格列酮和二甲双胍是否能改变NEFA诱导的2型糖尿病胰岛素抵抗，如果是的话，其作用机制。（葡萄糖类似于5.3 mmol/l，在吡格列酮治疗4个月之前和之后，在存在胰岛素-肝素（IL/H）或甘油的情况下进行胰岛素（与200 pmol/l相似）（n=11）或二甲双胍（n=9）。结果吡格列酮可增加IL/H过程中胰岛素刺激的葡萄糖消失（p < 0.01），增加胰岛素诱导的葡萄糖生成抑制（p < 0.01）、糖原分解抑制（p < 0.05）和糖原生成抑制（p < 0.05）。然而，在IL/H研究日，葡萄糖消失仍然较低（p <0.05），而葡萄糖产生（p < 0.01）、糖原生成（p < 0.05）和糖原分解（p < 0.05）高于甘油研究日，表明NEFA诱导的胰岛素抵抗持续存在。在IL/H过程中，二甲双胍使葡萄糖消失率增加（p < 0.001）至甘油治疗期间的速率，表明在肝外组织中对NEFA诱导的胰岛素抵抗具有保护作用。然而，葡萄糖的生产和代谢（但不是糖原分解）更高（p < 0.01）在IL/H比甘油治疗期间与二甲双胍，表明持久性NEFA诱导的肝insulin resistance.Conclusions/interpretation我们得出结论，吡格列酮改善肝和肝外胰岛素的作用，但不能防止NEFA诱导的胰岛素抵抗。相反，二甲双胍可预防NEFA诱导的肝外胰岛素抵抗，但不能预防NEFA诱导的肝胰岛素抵抗。
Aims/hypothesis We sought to determine whether pioglitazone and metformin alter NEFA-induced insulin resistance in type 2 diabetes and, if so, the mechanism whereby this is effected.Methods Euglycaemic-hyperinsulinaemic clamps (glucose similar to 5.3 mmol/l, insulin similar to 200 pmol/l) were performed in the presence of Intralipid-heparin (IL/H) or glycerol before and after 4 months of treatment with pioglitazone (n=11) or metformin (n=9) in diabetic participants. Hormone secretion was inhibited with somatostatin in all participants.Results Pioglitazone increased insulin-stimulated glucose disappearance (p < 0.01) and increased insulin-induced suppression of glucose production (p < 0.01), gluconeogenesis (p < 0.05) and glycogenolysis (p < 0.05) during IL/H. However, glucose disappearance remained lower (p < 0.05) whereas glucose production (p < 0.01), gluconeogenesis (p < 0.05) and glycogenolysis (p < 0.05) were higher on the IL/H study day than on the glycerol study day, indicating persistence of NEFA-induced insulin resistance. Metformin increased (p < 0.001) glucose disappearance during IL/H to rates present during glycerol treatment, indicating protection against NEFA-induced insulin resistance in extrahepatic tissues. However, glucose production and gluconeogenesis (but not glycogenolysis) were higher (p < 0.01) during IL/H than during glycerol treatment with metformin, indicating persistence of NEFA-induced hepatic insulin resistance.Conclusions/interpretation We conclude that pioglitazone improves both the hepatic and the extrahepatic action of insulin but does not prevent NEFA-induced insulin resistance. In contrast, whereas metformin prevents NEFA-induced extrahepatic insulin resistance, it does not protect against NEFA-induced hepatic insulin resistance.