Martins I J, Sainsbury A J, Mamo J C, Redgrave T G
Department of Physiology, University of Western Australia, Nedlands.
Diabetologia. 1994 Mar;37(3):238-46. doi: 10.1007/BF00398049.
In insulin-deficient streptozotocin-treated rats the intestine is hypertrophic and cholesterol synthesis and transport from the intestine are increased. The increased load of cholesterol is transported through the mesenteric lymph in chylomicrons. Clearance from plasma of injected chylomicrons is slowed in insulin-deficient rats, but the underlying mechanisms are currently unresolved. Hyperphagia may increase the size of chylomicrons which could contribute to defective chylomicron clearance in insulin-deficiency. In the present experiments we compared the size and number of chylomicrons in mesenteric lymph of control rats and diabetic rats infused with fat at two levels. In control and diabetic lymph-cannulated rats, as the infused dose of lipid increased the transport of triglyceride increased substantially compared with fasted rats. In contrast the transport of apoB48 increased by only a small amount during fat transport. Therefore, increased lipid transport was accomplished mostly by increased particle size, with only small increases in numbers of particles in intestinal lymph. Insulin-deficiency had no effect on triglyceride or apoB48 transport in lymph. Calculations suggested that each chylomicron particle contained a single molecule of apoB48. When hyperphagia in diabetic rats was prevented, the plasma triglycerides were decreased but the slow plasma clearance of injected chylomicron-like emulsions persisted. Hyperphagia, therefore, was unconnected to the impairment in chylomicron metabolism in insulin-deficient rats. Changes in the association with plasma apolipoproteins, in the expression of receptors for uptake of chylomicron remnants or in exposure to endothelial lipases may be responsible for the defective clearance of triacylglycerol-rich lipoproteins.
在链脲佐菌素诱导的胰岛素缺乏大鼠中，肠道出现肥大，肠道胆固醇合成及胆固醇转运增加。增加的胆固醇负荷以乳糜微粒的形式通过肠系膜淋巴进行转运。胰岛素缺乏的大鼠中，注射的乳糜微粒从血浆中的清除减慢，但其潜在机制目前尚未明确。摄食过多可能会增加乳糜微粒的大小，这可能导致胰岛素缺乏时乳糜微粒清除存在缺陷。在本实验中，我们比较了正常大鼠和在两个脂肪输注水平下的糖尿病大鼠肠系膜淋巴中乳糜微粒的大小和数量。在正常和糖尿病的淋巴插管大鼠中，与禁食大鼠相比，随着脂质输注剂量的增加，甘油三酯的转运显著增加。相比之下，在脂肪转运过程中载脂蛋白B48的转运仅少量增加。因此，脂质转运增加主要是通过颗粒大小增加实现的，肠道淋巴中颗粒数量仅少量增加。胰岛素缺乏对淋巴中甘油三酯或载脂蛋白B48的转运没有影响。计算表明，每个乳糜微粒颗粒含有单个载脂蛋白B48分子。当糖尿病大鼠的摄食过多被阻止时，血浆甘油三酯降低，但注射的乳糜微粒样乳剂的血浆清除减慢仍然存在。因此，摄食过多与胰岛素缺乏大鼠中乳糜微粒代谢受损无关。与血浆载脂蛋白结合的变化、乳糜微粒残粒摄取受体的表达变化或与内皮脂肪酶接触的变化可能是富含三酰甘油脂蛋白清除缺陷的原因。
