Insulin as a regulator of postprandial lipaemia in obesity

超重的人往往会患上心血管和外周血管疾病。原因是多方面的，但通常涉及脂肪代谢的紊乱。超重的受试者有在血液中积聚能量丰富的脂肪的趋势，这些脂肪来自肠道或肝脏。动脉长期暴露于这些脂质会导致某些类型的脂肪在血管壁上积聚，如果不减少，最终会导致血液流动障碍。我们实验室正在进行的研究发现，肥胖症患者这些脂肪的产生和清除受到干扰，可能是因为无法正确地对胰岛素做出反应。胰岛素激素对脂质的合成、分泌和清除起着关键的调节作用，然而，在肥胖者中，胰岛素浓度异常升高。我们探索了持续减肥对血液中脂质的产生和清除的影响。总的来说，减肥可以改善脂肪代谢，因为人们对胰岛素的正常作用更加敏感。然而，仅靠减肥很少能够完全纠正脂肪代谢的紊乱，而且个体很可能仍然有患血管疾病的风险。在这项提案中，我们希望探索两种药物的有效性，这两种药物可能通过增强胰岛素的调节作用来改善糖尿病患者的血脂紊乱。我们认为，长期纠正肥胖的血脂异常将减少心血管和外周血管疾病的频率和进展。

People who are overweight often develop cardio- and peripheral-vascular disease. The reasons are multifactorial but usually involve disturbances in the metabolism of fats. Overweight subjects have a tendency to accumulate energy rich lipids in blood derived from the gut or from the liver. Chronic arterial exposure to these lipids leads to an accumulation of certain types of fats in the wall of blood vessels, which if unabated ultimately leads to an impediment in blood flow. Ongoing studies in our laboratory have found that in obesity the production of these fats and the clearance is disturbed probably because of an inability to properly respond to insulin. The hormone insulin critically regulates synthesis, secretion and clearance of lipids, however, in obese subjects the concentration of insulin is abnormally elevated. We have explored the impact of sustained weight reduction on the production and clearance of lipids from blood. Collectively, weight loss leads to an improvement in fat metabolism because of increased sensitivity to the normal effects of insulin. However, weight reduction alone is rarely able to fully correct the disturbances in fat metabolism and it is likely that the individuals are still at risk of developing vascular disease. In this proposal, we wish to explore the efficacy of two agents which could potentially ameliorate lipid disturbances in diabetes by enhancing the regulatory effects of insulin. We believe that long term correction of the lipid abnormalities in obesity will reduce the frequency and progression of cardio- and peripheral-vascular disease.