| Autor: |
Wijesekara, Nadeeja, Ahrens, Rosemary, Wu, Ling, Langman, Tammy, Tandon, Anurag, Fraser, Paul E. |
| Předmět: |
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| Zdroj: |
Frontiers in Aging Neuroscience; 7/30/2021, Vol. 13, p1-9, 9p |
| Abstrakt: |
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 heightened 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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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