Trafficking of nonesterified fatty acids in insulin resistance and relationship to dysglycemia

Trafficking of nonesterified fatty acids in insulin resistance and relationship to dysglycemia
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DOI:
10.1152/ajpendo.00331.2019
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发表时间:
2020-03-01
影响因子:
5.1
通讯作者:
Shearer, Gregory C.
Shearer, Gregory C.
中科院分区:
医学2区
文献类型:
--
作者:
Walker, Rachel E.;Ford, Jennifer L.;Shearer, Gregory C.

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在脂肪中,胰岛素的作用是抑制细胞内脂肪分解和非酯化脂肪酸 (NEFA) 分泌到血浆中。我们在频繁采样的静脉内葡萄糖耐量试验 (FSIVGTT) 后应用葡萄糖和 NEFA 最小模型 (MM) 来评估葡萄糖特异性和 NEFA 特异性胰岛素抵抗。我们在 NEFA MM 中使用总 NEFA 和单个脂肪酸,将代谢综合征 (MetSyn) 受试者 (n = 52) 与最佳健康对照 (OptHC; n = 14) 的模型参数进行比较。结果报告为平均差(95% 置信区间)。使用葡萄糖 MM,MetSyn 受试者对胰岛素 (Si) 的敏感性较低 [-73% (- 82, -57)],而对葡萄糖 (AIRg) 的急性胰岛素反应较高 [138% (44, 293)]。使用 NFFA MM,MetSyn 受试者具有较低的 er [ - 24% ( -35, -13)] 百分比抑制、较高的 [32% (15, 52)] 阈值葡萄糖 (gs) 和较高的 [81% (12, 192)] 改变 NEFA 分泌的亲和常数 (d>)。与脂肪酸相比,肉豆蔻酸 (M A) 的抑制百分比低于所有其他脂肪酸,并且硬脂酸 (SA) 的反应非常独特,以至于它不会影响 NEFA MM。注射葡萄糖后 50 分钟,MA 和 SA 占总量的百分比增加,而油酸 (OA) 和棕榈酸 (PA) 减少 (P < 0.05)。我们得出的结论是,OptHC 和 MetSyn 受试者之间的 NEFA MM 以及 FSIV GTT 后各个 NEFA 脂肪酸的反应不同,并且各个脂肪酸之间的 NEFA MM 参数也不同。
In adipose, insulin functions to suppress intracellular lipolysis and secretion of nonesterified fatty acid (NEFA) into plasma. We applied glucose and NEFA minimal models (MM) following a frequently sampled intravenous glucose tolerance test (FSIVGTT) to assess glucose-specific and NEFA-specific insulin resistance. We used total NEFA and individual fatty acids in the NEFA MM, comparing the model parameters in metabolic syndrome (MetSyn) subjects (n = 52) with optimally healthy controls (OptHC; n = 14). Results are reported as mean difference (95% confidence interval). U sing the glucose MM, MetSyn subjects had low er [ -73% (- 82, -57)] sensitivity to insulin (Si) and higher [138% (44, 293)] acute insulin response to glucose (AIRg). Using the NFFA MM, MetSyn subjects had low er [ - 24% ( -35, -13)] percent suppression, higher [32% (15, 52)] threshold glucose (gs), and a higher [81% (12, 192)] affinity constant altering NEFA secretion (d>). Comparing fatty acids, percent suppression was low er in myristic acid (M A) than in all other fatty acids, and the stearic acid (SA) response was so unique that it did not tit the NEFA MM. MA and SA percent of total were increased at 50 min after glucose injection, whereas oleic acid (OA) and palm itic acid (PA) were decreased (P < 0.05). We conclude that the NEFA MM, as w ell as the response of individual NEFA fatty acids after a FSIV GTT, differ between OptHC and MetSyn subjects and that the NEFA MM parameters differ between individual fatty acids.