EAPSI: Transport of Chromium(III) Under Elevated Glycemic Conditions in Vivo

人们对治疗糖尿病非常感兴趣，包括铬（Cr）减轻其症状的潜力。由于糖尿病患者体内葡萄糖过剩，血清蛋白的糖基化程度比正常人更大，对宿主产生不利影响。先前铁转运蛋白转铁蛋白（Tf）的糖基化已被证明可以改变其功能。由于转铁蛋白也将铬从血液转运到组织，因此转铁蛋白的糖基化也可能显著影响铬向组织的转运；然而，这些影响到目前为止还没有被研究过。该奖项支持利用啮齿动物模型系统探索转铁蛋白糖基化对铬（III）摄取的影响。这项研究将在国立中兴大学进行，由研究铬对模型啮齿动物系统影响的专家Frank Moa博士和wenying Chen博士指导。本项目将探讨转铁蛋白糖基化对健康、1型和2型糖尿病动物模型中铬（III）摄取的影响。糖尿病是一个世界性的问题，铬（III）是一种潜在的治疗这种疾病症状的药物，已经得到了相当的关注。铬（III）已被证明可以增加胰岛素敏感性，改善糖尿病啮齿动物模型中的胆固醇和甘油三酯水平。糖尿病的一个副作用是血糖水平升高。由于血糖水平升高，血清蛋白会发生不可逆的糖基化。糖基化可以改变这些蛋白质的性质和功能，包括铁转运蛋白转铁蛋白。转铁蛋白不仅在血液中携带铁，而且似乎是将铬（III）从血液转运到组织的唯一媒介。因此，糖尿病患者转铁蛋白的糖基化可以改变铬（III）转移到组织的能力，从而增加组织中的胰岛素敏感性。该奖项由美国国家科学基金会EAPSI与台湾科学技术部合作资助，支持一名美国研究生的研究。

Significant interest exists in treating diabetes, including the potential of chromium (Cr) to reduce its symptoms. As diabetics have a surplus of glucose in their bodies, blood serum proteins can be glycosylated to a greater extent than normal, resulting in detrimental effects on the hosts. Previously glycosylation of the iron transport protein transferrin (Tf) has shown to alter its function. As transferrin also transports chromium from the bloodstream to tissues, glycosylation of transferrin may also significantly affect chromium transport to the tissues; however, these effects have not been examined to date. This award supports research to explore the effect of glycosylation of transferrin on the uptake of chromium(III) using a rodent model system. The research will be conducted at National Chung Hsing University under the mentorship of Dr. Frank Moa and Dr. Wen-Ying Chen, experts in the effects of chromium in model rodent systems.This project will explore the effect of glycosylation of transferrin on the uptake of chromium(III) in healthy, type 1, and type 2 diabetic animal models. Diabetes is a worldwide problem, and a potential therapeutic agent to treat symptoms of this disease that has received appreciable attention is chromium(III). Chromium(III) has been shown to increase insulin sensitivity and improve cholesterol and triglyceride levels in rodent models of diabetes. One side effect of diabetes is increased blood glucose levels. As a result of the higher glucose levels, blood serum proteins can become irreversibly glycosylated. Glycosylation can alter the properties and functions of these proteins, including the iron transport protein transferrin. Transferrin not only carries iron in the bloodstream but also appears to be the sole agent that transports chromium(III) from the bloodstream to the tissues. Thus, glycosylation of transferrin of diabetic subjects could alter the ability for chromium(III) to be transferred to tissues and thus increase insulin sensitivity in tissues. This NSF EAPSI award supports the research of a U.S. graduate student and is funded in collaboration with the Ministry of Science and Technology of Taiwan.