Adipocytes in subjects with impaired fasting glucose and impaired glucose tolerance are resistant to the anti-lipolytic effect of insulin
Adipocytes in subjects with impaired fasting glucose and impaired glucose tolerance are resistant to the anti-lipolytic effect of insulin
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DOI：
10.1007/s00592-008-0033-z
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发表时间：
2008-09-01
影响因子：
3.8
通讯作者：
DeFronzo, Ralph A.
中科院分区：
文献类型：
--
作者：
Abdul-Ghani, Muhammad A.;Molina-Carrion, Marjorie;DeFronzo, Ralph A.
空腹血糖受损 (IFG) 和糖耐量受损 (IGT) 是从正常糖代谢转变为 2 型糖尿病的两种中间状态。胰岛素钳夹研究表明，患有 IGT 的受试者骨骼肌中的胰岛素抵抗增加，而患有 IFG 的受试者则具有接近正常的肌肉胰岛素敏感性。由于游离脂肪酸 (FFA) 代谢的改变在胰岛素抵抗的发病机制中起着核心作用，我们检查了 IGT 和 IFG 受试者在禁食条件下以及 OGTT 期间的血浆游离脂肪酸浓度。研究了 71 名 NGT、70 名 IGT 和 46 名 IFG 受试者。 IGT 受试者的空腹血浆 FFA 显着高于 NGT，而 IFG 受试者的空腹血浆 FFA 浓度与 NGT 相似。然而，与 NGT 相比，IFG 受试者的空腹血浆胰岛素浓度显着升高，而 IGT 受试者的空腹血浆胰岛素水平接近正常。与 NGT 相比，IFG 和 IGT 受试者的脂肪细胞胰岛素抵抗指数（空腹血浆 FFA 和 FPI 的乘积）均显着增加。在 OGTT 期间，与 NGT 受试者类似，IFG 和 IGT 受试者均抑制了血浆 FFA 浓度，但 IFG 和 IGT 受试者的血糖后负荷显着增加。这些数据表明，患有 IFG 和 IGT 的受试者对胰岛素的抗脂解作用的抵抗力增加。然而，在基础条件下，IFG受试者的空腹高胰岛素血症足以抵消脂肪细胞胰岛素抵抗并维持正常的空腹血浆FFA浓度，而IGT受试者的FPI缺乏增加导致空腹血浆FFA升高。
Impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) are two intermediate states in the transition from normal glucose metabolism to type 2 diabetes. Insulin clamp studies have shown that subjects with IGT have increased insulin resistance in skeletal muscle, while subjects with IFG have near normal muscle insulin sensitivity. Because of the central role of altered free fatty acid (FFA) metabolism in the pathogenesis of insulin resistance, we have examined plasma free fatty acid concentration under fasting conditions, and during OGTT in subjects with IGT and IFG. Seventy-one NGT, 70 IGT and 46 IFG subjects were studied. Fasting plasma FFA in IGT subjects was significantly greater than NGT, while subjects with IFG had similar fasting plasma FFA concentration to NGT. However, fasting plasma insulin concentration was significantly increased in IFG subjects compared to NGT while subjects with IGT had near normal fasting plasma insulin levels. The adipocyte insulin resistance index (product of fasting plasma FFA and FPI) was significantly increased in both IFG and IGT subjects compared to NGT. During the OGTT both IFG and IGT subjects suppressed their plasma FFA concentration similarly to NGT subjects, but the post-glucose loads were significantly increased in both IFG and IGT subjects. These data suggest that both subjects with IFG and IGT have increased resistance to the antilipolytic action of insulin. However, under basal conditions, fasting hyperinsulinemia in IFG subjects is sufficient to offset the adipocyte insulin resistance and maintain normal fasting plasma FFA concentration while the lack of increase in FPI in IGT subjects results in an elevated fasting plasma FFA.