التفاصيل البيبلوغرافية
| العنوان: |
α-Synuclein Regulates Peripheral Insulin Secretion and Glucose Transport |
| المؤلفون: |
Wijesekara, Nadeeja, Ahrens, Rosemary, Wu, Ling, Langman, Tammy, Tandon, Anurag, Fraser, Paul E. |
| المساهمون: |
Canadian Institutes of Health Research, Alzheimer's Society |
| المصدر: |
Frontiers in Aging Neuroscience ; volume 13 ; ISSN 1663-4365 |
| بيانات النشر: |
Frontiers Media SA |
| سنة النشر: |
2021 |
| المجموعة: |
Frontiers (Publisher - via CrossRef) |
| مصطلحات موضوعية: |
Cognitive Neuroscience, Aging |
| الوصف: |
Aim Population based studies indicate a positive association between type 2 diabetes (T2D) and Parkinson’s disease (PD) where there is an increased risk of developing PD in patients with T2D. PD is characterized by the abnormal accumulation of intraneuronal aggregated α-synuclein (α-syn) in Lewy bodies, which negatively impact neuronal viability. α-syn is also expressed in both pancreatic islets and skeletal muscle, key players in glucose regulation. Therefore, we examined the functional role of α-syn in these tissues. Methods Using mice lacking, overexpressing or transiently injected with α-syn, effects on glucose and insulin tolerance and insulin secretion were determined, with further characterization of the effects on GLUT4 translocation using GLUT4 myc myotubes. Results Mice genetically ablated for α-syn became glucose intolerant and insulin resistant with hyperinsulinemia and reduced glucose-stimulated insulin secretion (GSIS). Mice overexpressing human α-syn are more insulin senstive and glucose tolerant compared to controls with increased GSIS. Injection of purified α-syn monomers also led to improved glucose tolerance and insulin sensitivity with hightened GSIS. α-syn monomer treatments increased surface GLUT4 levels in myotubes but without any significant change in Akt phosphorylation. The increase in cell surface GLUT4 was largely due to a large reduction in GLUT4 endocytosis, however, with a compensatory reduction in GLUT4 exocytosis. Conclusion Cumulatively, this data suggests that α-syn modulates both pancreatic beta cell function and glucose transport in peripheral tissues, thereby playing a pivitol role in the maintenance of normal glucose homeostasis. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
unknown |
| DOI: |
10.3389/fnagi.2021.665348 |
| DOI: |
10.3389/fnagi.2021.665348/full |
| الإتاحة: |
https://doi.org/10.3389/fnagi.2021.665348Test |
| حقوق: |
https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: |
edsbas.58774468 |
| قاعدة البيانات: |
BASE |
