The central hypothesis to be tested in this proposal is that the development of Type 2 diabetes induces alterations in the protein composition of lipid rafts in monocytes and in lipoproteins. Furthermore, we hypothesize that these changes will serve as biomarkers for both the development of diabetes (pre-diabetic to diabetic transition) and serve as biomarkers for the development of subsequent cardiovascular complications. The goal of this proposal is to elucidate proteins that are altered in monocyte lipid rafts and lipoproteins in patients with impaired glucose tolerance and newly diagnosed type 2 diabetics compared to patients with normal glucose tolerance. A unique aspect of this proposal is the use of pediatric patients. Type 2 diabetes has historically been an adult disease but unfortunately a large and growing number of children have type 2 diabetes. Although the mechanisms and progression of the disease appear similar in adults and children, a major difference between adult and pediatric patients is that the pediatric patients do not have as extensive co-morbidities such as atherosclerosis, renal failure, and neuropathy. A major problem in identifying biomarkers for type 2 diabetes are confounds created by patients having multiple diseases and taking multiple medications. For the most part these confound is not a major problem in pediatric patients. For these reasons, we have chosen to use pediatric patients.
Three Specific Aims are proposed.
Aim 1 : To elucidate the complete proteome of lipid rafts in monocytes and in isolated lipoproteins (LDL and HDL) isolated from patients with normal glucose tolerance.
Aim 2 : To identify a subset of proteins that associate or disassociate with lipid rafts in monocytes and in lipoproteins (LDL and HDL) isolated from patients with impaired glucose tolerance.
Aim 3 : To characterize the proteome of lipid rafts in monocytes and in lipoproteins (LDL and HDL) isolated from newly diagnosed Type 2 diabetics. ? ? ? ?
| Zhai, Jianjun; Ström, Anna-Lena; Kilty, Renee et al. (2009) Proteomic characterization of lipid raft proteins in amyotrophic lateral sclerosis mouse spinal cord. FEBS J 276:3308-23 |
