Insulin as a regulator of postprandial lipaemia in obesity

超重的人经常会患上心血管和外周血管疾病。原因是多方面的，但通常与脂肪代谢紊乱有关。超重的人倾向于在血液中积累来自肠道或肝脏的富含能量的脂质。动脉长期暴露在这些脂质中会导致某些类型的脂肪在血管壁上积累，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，在肥胖中，这些脂肪的产生和清除受到干扰，可能是因为无法对胰岛素做出适当的反应。激素胰岛素对脂质的合成、分泌和清除起着关键的调节作用，然而，肥胖受试者的胰岛素浓度异常升高。我们探索了持续减肥对血液中脂质产生和清除的影响。总的来说，减肥会导致脂肪代谢的改善，因为对胰岛素正常作用的敏感性增加了。然而，仅靠减肥很少能完全纠正脂肪代谢的紊乱，而且很可能这些人仍有患血管疾病的风险。在这个提议中，我们希望探索两种药物的功效，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的脂质紊乱。我们认为，长期纠正肥胖的脂质异常将减少心血管和外周血管疾病的发生频率和进展。

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.