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β-Cell-Specific Glucocorticoid Reactivation Attenuates Inflammatory β-Cell Destruction
Xiaoxia Liu1, Sophie Turban2, Roderick N Carter2
1Molecular Metabolism Group, University/BHF Centre for Cardiovascular Science, Queen's Medical Research Institute , Edinburgh , UK ; Division of Endocrinology and Metabolism, Department of Internal Medicine, Huashan Hospital, Shanghai Medical College, Fudan University , Shanghai , China.
Frontiers in Endocrinology
|October 30, 2014
Summary
Targeting 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) in pancreatic beta cells may protect against type 1 diabetes. This approach could improve beta cell survival and insulin levels, offering new therapeutic strategies.
Area of Science:
- Endocrinology
- Immunology
- Diabetes Research
Background:
- Type 1 diabetes progression involves inflammation and nitric oxide-induced beta-cell damage.
- High-dose glucocorticoids (GCs) are unsuitable for type 1 diabetes due to insulin resistance and suppressed secretion.
- Physiological GC action in beta cells can prevent lipotoxic failure.
Purpose of the Study:
- To investigate if elevated beta-cell 11beta-HSD1 protects against streptozotocin (STZ)-induced beta-cell destruction.
- To assess the impact of enhanced 11beta-HSD1 on hyperglycemia, beta-cell survival, and immune response in type 1 diabetes models.
Main Methods:
- Utilized transgenic mice overexpressing 11beta-HSD1 in beta cells (MIP-HSD1(tg/+)).
- Administered single high-dose or multiple low-dose streptozotocin (STZ) to induce diabetes-like conditions.
- Assessed beta-cell survival, replication, insulin levels, insulitis, macrophage infiltration, and nitric oxide production in vitro and in vivo.
Main Results:
- MIP-HSD1(tg/+) mice showed episodic protection from high-dose STZ-induced hyperglycemia, with improved beta-cell survival and function.
- These mice exhibited reduced inflammation, increased regulatory T cells, and attenuated nitric oxide production.
- MIP-HSD1(tg/+) mice were resistant to low-dose STZ-induced hyperglycemia and insulitis.
Conclusions:
- Selective GC regeneration within beta cells via 11beta-HSD1 protects against inflammatory beta-cell destruction.
- Targeting 11beta-HSD1 presents a potential therapeutic strategy for type 1 diabetes and islet transplantation.
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