Tomita T, Yamasaki Y, Kubota M, Tohdo R, Katsura M, Ikeda M, Nakahara I, Shiba Y, Matsuhisa M, Hori M
First Department of Medicine, Osaka University School of Medicine, Japan.
Endocr J. 1998 Apr;45(2):165-73. doi: 10.1507/endocrj.45.165.
It has been proposed that high plasma free fatty acid (FFA) levels observed in patients with non-insulin dependent diabetes mellitus (NIDDM) contribute to the development of their insulin resistance. We examined patients with NIDDM to find whether maintaining plasma FFA levels in the fasting range with a euglycemic hyperinsulinemic clamp combined with an oral glucose load (clamp OGL) would affect insulin-mediated peripheral glucose uptake (PGU) and splanchnic glucose uptake (SGU). Nine NIDDM subjects (age, 55 +/- 3 years; duration of diabetes, 11 +/- 2 years; body mass index, 21.0 +/- 0.4 kg/m2; hemoglobin A1c, 9.0 +/- 0.3%; fasting plasma glucose, 9.4 +/- 3.0 mmol/l, means +/- SEM) were hospitalized and treated with diet, oral hypoglycemic agents or insulin for at least 2 weeks to maintain fasting plasma glucose < 8 mmol/l. All the patients were subjected to two different protocols in a random order. On one protocol, under the hyperinsulinemic condition, FFAs were maintained at the their fasting levels (1.19 +/- 0.08) by triglyceride emulsion infusion (Lipid infusion study, L), and on the other protocol, FFAs were made to fall (0.26 +/- 0.06 mmol/l) with saline instead of triglyceride emulsion infusion (Saline infusion study, S). During euglycemic (L, 5.4 +/- 0.2; S, 5.1 +/- 0.2 mmol/l) hyperinsulinemic (L, 1377 +/- 108; S, 1328 +/- 67 pmol/l) clamp, high FFA levels significantly reduced PGU (L, 26.7 +/- 3.6; S, 32.1 +/- 3.4 mumol.kg-1.min-1, P < 0.05) and SGU (L, 12.1 +/- 4.2; S, 27.5 +/- 5.6%, P < 0.05). In conclusion, high FFA levels in patients with NIDDM impaired insulin-mediated glucose uptake in the splanchnic as well as peripheral tissues.
有人提出，非胰岛素依赖型糖尿病（NIDDM）患者中观察到的高血浆游离脂肪酸（FFA）水平会导致其胰岛素抵抗的发展。我们对NIDDM患者进行了检查，以确定通过正常血糖高胰岛素钳夹联合口服葡萄糖负荷（钳夹OGL）将空腹血浆FFA水平维持在正常范围内是否会影响胰岛素介导的外周葡萄糖摄取（PGU）和内脏葡萄糖摄取（SGU）。9名NIDDM受试者（年龄55±3岁；糖尿病病程11±2年；体重指数21.0±0.4kg/m²；糖化血红蛋白9.0±0.3%；空腹血浆葡萄糖9.4±3.0mmol/l，均值±标准误）住院，接受饮食、口服降糖药或胰岛素治疗至少2周，以维持空腹血浆葡萄糖<8mmol/l。所有患者按随机顺序接受两种不同方案。在一种方案中，在高胰岛素血症条件下，通过输注甘油三酯乳剂将FFA维持在空腹水平（1.19±0.08）（脂质输注研究，L），在另一种方案中，用生理盐水代替甘油三酯乳剂输注使FFA下降（0.26±0.06mmol/l）（生理盐水输注研究，S）。在正常血糖（L组5.4±0.2；S组5.1±0.2mmol/l）高胰岛素血症（L组1377±108；S组1328±67pmol/l）钳夹期间，高FFA水平显著降低了PGU（L组26.7±3.6；S组32.1±3.4μmol·kg⁻¹·min⁻¹，P<0.05）和SGU（L组12.1±4.2；S组27.5±5.6%，P<0.05）。总之，NIDDM患者的高FFA水平损害了胰岛素介导的内脏和外周组织葡萄糖摄取。
