| Autor: |
Afaf Absood, Benjamin Gandomani, Anthony Zaki, Vlad Nasta, Andrew Michail, Peter M W Habib, Israel Hodish |
| Jazyk: |
angličtina |
| Rok vydání: |
2013 |
| Předmět: |
|
| Zdroj: |
PLoS ONE, Vol 8, Iss 2, p e54351 (2013) |
| Druh dokumentu: |
article |
| ISSN: |
1932-6203 |
| DOI: |
10.1371/journal.pone.0054351 |
| Popis: |
Insulin therapy improves β-cell function in early stages of diabetes by mechanisms that may exceed alleviation of glucotoxicity. In advance type 2 diabetes, hyperglycemia causes β-cell damage and ultimately β-cell loss. At such an advanced stage, therapeutic modalities are often inadequate. Growing evidence indicates that in early stages of type-2 diabetes and some types of monogenic diabetes linked with malfunctioning endoplasmic-reticulum (ER), the β-cell ER fails to process sufficient proinsulin once it becomes overloaded. These changes manifest with ER distention (ER-crowding) and deficiency of secretory granules. We hypothesize that insulin therapy may improves β-cell function by alleviating ER-crowding. To support this hypothesis, we investigated pre-diabetic β-cell changes in hProC(A7)Y-CpepGFP transgenic mice that develop prolonged pre-diabetes due to proinsulin dysmaturation and ER-crowding. We attenuated the β-cell ER proinsulin synthesis with a treat-to-target insulin therapy while avoiding hypoglycemia and weight gain. Alleviation of ER-crowding resulted in temporary improvement in proinsulin maturation, insulin secretion and glucose tolerance. Our observations suggest that alleviation of pre-diabetic ER-crowding using a treat-to-target insulin therapy may improve β-cell function and may prevent further metabolic deterioration. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
