β-Cell preservation and regeneration in diabetes by modulation of β-cell Ca2+ homeostasis
| Autor: | Evrard Nguidjoe, Lin Jiang, Nathalie Pachera, André Herchuelz |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
geography
medicine.medical_specialty geography.geographical_feature_category biology business.industry Endocrinology Diabetes and Metabolism Insulin medicine.medical_treatment Endoplasmic reticulum ATPase Islet Transplantation Endocrinology Apoptosis Internal medicine Internal Medicine medicine Unfolded protein response biology.protein Plasma membrane Ca2+ ATPase business |
| Zdroj: | Diabetes, Obesity and Metabolism. 14:136-142 |
| ISSN: | 1462-8902 |
| DOI: | 10.1111/j.1463-1326.2012.01649.x |
| Popis: | Ca(2+) extrusion from the β-cell is mediated by two processes the Na/Ca exchanger (NCX) and the plasma membrane Ca(2+) -ATPase (PMCA). Gain of function studies show that overexpression of NCX or PMCA leads to endoplasmic reticulum (ER) Ca(2+) depletion with subsequent ER stress, decrease in β-cell proliferation and β-cell death by apoptosis. Interestingly, chronic exposure to cytokines or high free fatty acid concentrations also induce ER Ca(2+) depletion and β-cell death in diabetes. Loss of function studies show, on the contrary, that heterozygous inactivation of NCX1 (Ncx1(+/-)) leads to an increase in β-cell function (insulin production and release), and a fivefold increase in both β-cell mass and proliferation. The mutation also increases β-cell resistance to hypoxia, and Ncx1(+/-) islets show a two to four times higher rate of diabetes cure than Ncx1(+/+) islets when transplanted in diabetic animals. Thus, down-regulation of the Na/Ca exchanger leads to various changes in β-cell function that are opposite to the major abnormalities seen in diabetes. This provides a unique model for the prevention and treatment of β-cell dysfunction in diabetes and following islet transplantation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text