Saloranta C, Groop L, Ekstrand A, Franssila-Kallunki A, Taskinen M R
Fourth Department of Medicine, Helsinki University Hospital, Finland.
Acta Diabetol. 1994 Apr;31(1):6-13. doi: 10.1007/BF00580753.
Hypertriglyceridaemia is associated with insulin resistance of both lipid and glucose metabolism. It is not known whether the insulin resistance affects both glucose oxidation and glycogen formation. To study the oxidative and non-oxidative pathways of non-esterified fatty acids (NEFA) and glucose metabolism, eight male hypertriglyceridaemic subjects were studied during insulin infusion (75 and 340 pmol/m2.min) in combination with indirect calorimetry and infusions of [3-3H]glucose and [1-14C]palmitate before and after 4 weeks of treatment with the antilipolytic agent acipimox (250 mg three times daily). Compared with eight healthy subjects the hypertriglyceridaemic subjects were resistant to the antilipolytic effect of insulin, both in the basal state (P < 0.05) and during insulin infusion (P < 0.05). This was associated with impaired insulin-stimulated glucose uptake (P < 0.05), predominantly in the non-oxidative pathway (P < 0.05). Acipimox decreased basal NEFA concentrations (P < 0.01) and reduced lipid oxidation during low-dose insulin infusion (P < 0.05). Glucose uptake, predominantly glycogen formation, was stimulated by acipimox (P < 0.05). In conclusion, the insulin resistance of glucose metabolism associated with hypertriglyceridaemia is largely due to a defect in non-oxidative glucose metabolism. Acipimox improves glucose metabolism both by affecting glucose oxidation (low-dose insulin) and non-oxidative glucose metabolism (high-dose insulin).
高甘油三酯血症与脂质和葡萄糖代谢的胰岛素抵抗相关。目前尚不清楚胰岛素抵抗是否会影响葡萄糖氧化和糖原形成。为了研究非酯化脂肪酸（NEFA）和葡萄糖代谢的氧化和非氧化途径，对8名男性高甘油三酯血症患者在输注胰岛素（75和340 pmol/m²·分钟）期间进行了研究，同时结合间接测热法，并在使用抗脂解药物阿西莫司（250 mg，每日三次）治疗4周前后输注[3-³H]葡萄糖和[1-¹⁴C]棕榈酸酯。与8名健康受试者相比，高甘油三酯血症患者在基础状态（P < 0.05）和胰岛素输注期间（P < 0.05）对胰岛素的抗脂解作用均有抵抗。这与胰岛素刺激的葡萄糖摄取受损有关（P < 0.05），主要在非氧化途径（P < 0.05）。阿西莫司降低了基础NEFA浓度（P < 0.01），并在低剂量胰岛素输注期间降低了脂质氧化（P < 0.05）。阿西莫司刺激了葡萄糖摄取，主要是糖原形成（P < 0.05）。总之，与高甘油三酯血症相关的葡萄糖代谢胰岛素抵抗主要是由于非氧化葡萄糖代谢缺陷。阿西莫司通过影响葡萄糖氧化（低剂量胰岛素）和非氧化葡萄糖代谢（高剂量胰岛素）来改善葡萄糖代谢。
