Mechanisms of fatty-acid mediated destruction of pancreatic beta cells

2型糖尿病与肥胖有关，但并非所有肥胖者都会患上这种疾病。非糖尿病性肥胖受试者能够通过朗格汉斯岛胰岛β细胞的胰岛素输出增加来补偿对胰岛素敏感性的降低（肥胖的一般特征）。在糖尿病患者中，这种代偿机制被破坏。肥胖和2型糖尿病也与血液中脂肪酸（FAs）水平升高有关。这些可以被β细胞吸收，并在那里发挥短期和长期的作用。长期来看，FAs可能对β细胞有毒性，这被认为是β细胞代偿失败的重要原因。该项目旨在更好地了解不同类型的FAs影响β细胞对破坏的易感性的方式。它建立在我们的初步结果的基础上，表明β细胞将饱和脂肪酸转化为不饱和脂肪酸的能力有助于保护它们免受破坏。我们的目的是研究这种保护背后的机制。

Type 2 diabetes is associated with obesity, but not all obese individuals develop the disease. Non-diabetic obese subjects are able to compensate for diminished sensitivity to insulin (a general feature of obesity) by enhanced output of insulin from the pancreatic beta-cells of the islet of Langerhans. In diabetics this compensatory mechanism is disrupted. Obesity and Type 2 diabetes are also associated with elevated levels of fatty acids (FAs) in the bloodstream. These can be taken up by the beta-cells where they exert both short and long-term effects. In the longer term FAs can be toxic to beta-cells and this is thought to be important in the failure of beta-cell compensation. The project is aimed at a better understanding of the manner by which different types of FAs influence the susceptibility of beta-cells to destruction. It builds on our preliminary results suggesting that the capacity of the beta-cell to convert saturated FAs to unsaturated FAs helps protect them from destruction. Our aim is to examine the mechanisms underlying this protection.