The role of CPR-1 in type 2 diabetes and pancreatic β-cell function in vivo
| Autor: | Shuo-Wen Hsu, 徐碩彣 |
|---|---|
| Rok vydání: | 2015 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 103 Type 2 Diabetes (T2D) is characterized by insulin deficiency and insulin resistance, leading to aberrant homeostasis of glucose, protein and lipid. Consequently, can develop cardiovascular diseases, retinopathy, neuropathy, nephropathy, foot ulcers, etc. Genetic and environmental factors are the primary causes of diabetes. International Diabetes Federation estimated that 400 million people are afflicted with this disease worldwide. Current anti-diabetic agents, which target insulin resistance, insulin secretion and glucose control, fail to cure T2D. Therefore, seeking new approaches to cure T2D is still on urgent demand. More recently, loss of functional β-cells is thought as a pathological factor in T2D. Despite numerous anti-diabetic medications available, none of them can effectively suppress β-cell failure. CPR-1 belongs to protein disulfide isomerase family. In our previous study, CPR-1 is primarily expressed in pancreas and islets, and up-regulated in β cells and serum in response to metabolic stress. To further decipher the importance of CPR1 in β-cell function and T2D, we generated CPR1 knockout (CPR1 KO) mice. CPR1 KO mice showed no noticeable phenotypes on B6 background. We then crossed CPR1 KO mice into Leprdb/db background. Surprisingly, around 40% of CPR-1 KO Leprdb/db mice were diabetes-free and the rest (60%) developed borderline diabetes as evidenced by blood glucose, hemoglobin A1C, glucose intolerance and β-cell function. Moreover, T2D in CPR-1 KO Leprdb/db mice with borderline diabetes can be reversed after 8-week treatment with metformin, and so does the older CPR-1 KO Leprdb/db. In conclusion, CPR-1 could suppress T2D probably via regulation of β-cell function and preservation. To together with reduced insulin resistance completely reversed T2D in diabetic mouse models. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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